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Xie L, Wang Y, Wan A, Huang L, Wang Q, Tang W, Qi X, Hu X. Research trends of neoadjuvant therapy for breast cancer: A bibliometric analysis. Hum Vaccin Immunother 2025; 21:2460272. [PMID: 39904891 PMCID: PMC11801352 DOI: 10.1080/21645515.2025.2460272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 01/06/2025] [Accepted: 01/25/2025] [Indexed: 02/06/2025] Open
Abstract
The approach of neoadjuvant therapy for breast cancer, which involves administering systemic treatment prior to primary surgery, has undergone substantial advancements in recent decades. This strategy is intended to reduce tumor size, thereby enabling less invasive surgical procedures and enhancing patient outcomes. This study presents a comprehensive bibliometric analysis of research trends in neoadjuvant therapy for breast cancer from 2009 to 2024. Using data extracted from the Web of Science Core Collection, a total of 3,674 articles were analyzed to map the research landscape in this field. The analysis reveals a steady increase in publication output, peaking in 2022, with the United States and China identified as the leading contributors. Key institutions, such as the University of Texas System and MD Anderson Cancer Center, have been instrumental in advancing the research on neoadjuvant therapy. The study also highlights the contributions of influential authors like Sibylle Loibl and Gunter von Minckwitz, as well as major journals such as the Journal of Clinical Oncology. Emerging research topics, including immunotherapy, liquid biopsy, and artificial intelligence, are gaining prominence and represent potential future directions for clinical applications. This bibliometric analysis provides critical insights into global research trends, key contributors, and future developments in the field of neoadjuvant therapy for breast cancer, offering a foundation for future research and clinical practice advancements.
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Affiliation(s)
- Laiping Xie
- Department of Nuclear Medicine, Southwest Hospital, Army Medical University, Chongqing, China
| | - Yuhang Wang
- Department of Gastroenterology, Beijing Children’s Hospital, Capital Medical University, Beijing, China
| | - Andi Wan
- Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Key Laboratory of Chongqing Health Commission for Minimally Invasive and Precise Diagnosis, Chongqing, China
| | - Lin Huang
- Department of Radiology, People’s Hospital of Xingyi, Guizhou, China
| | - Qing Wang
- Institute of Medical Information, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wanyan Tang
- Department of Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
| | - Xiaowei Qi
- Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Key Laboratory of Chongqing Health Commission for Minimally Invasive and Precise Diagnosis, Chongqing, China
| | - Xiaofei Hu
- Department of Nuclear Medicine, Southwest Hospital, Army Medical University, Chongqing, China
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Nierenberg TC, Thomas SM, Halliday I, Botty van den Bruele A, Chiba A, Modell Parrish KJ, Woriax HE, DiNome ML, Westbrook KE, Plichta JK. Survival outcomes after pathologic complete response with neoadjuvant endocrine therapy vs. neoadjuvant chemotherapy: a retrospective national database study. Breast Cancer Res Treat 2025; 212:161-172. [PMID: 40349259 PMCID: PMC12118946 DOI: 10.1007/s10549-025-07717-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Accepted: 05/01/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND Neoadjuvant therapies can result in pathologic complete response (pCR) in patients with breast cancer, which can be predictive of long-term outcomes. Patients with estrogen receptor positive (ER +) tumors may receive either neoadjuvant chemotherapy (NAC) or neoadjuvant endocrine therapy (NET). We sought to compare survival outcomes in those with non-metastatic ER + breast cancer who received NET or NAC and achieved pCR. METHODS All patients diagnosed with ER + /HER2- stage I-III breast cancer, who received neoadjuvant systemic therapy followed by surgery, and achieved pCR, were selected from the National Cancer Database (NCDB, 2010-2021). The Kaplan-Meier method was used to estimate overall survival (OS), and log-rank tests were used to test for differences in OS. Cox Proportional Hazards models were used to estimate the association of NAC vs NET with OS, after adjustment for covariates. RESULTS 3313 patients met eligibility criteria: 3148 received NAC and 165 NET. The median follow-up for the entire cohort was 82 months (95% CI 80.4-83.1). Patients who received NAC were significantly younger (median age: NAC 49y vs NET 64y; p < 0.001), more likely to have a comorbidity score of 0 (NAC 89.3% vs NET 81.2%, p = 0.004), and more likely to have private insurance (NAC 68.9% vs NET 44.2%, p < 0.001). There were no significant differences between the NAC and NET patients based on race and ethnicity, income, education, or community type (all p > 0.05). The NAC treated patients were more likely to have larger tumors [median tumor size (IQR): NAC 3 cm (2.0-4.3) vs NET 1.3 cm (0.7-2.8); p < 0.001)], ductal histology (NAC 92.6% vs 81.2%, p < 0.001), and grade 3 tumors (NAC 70.2% vs 10.3%, p < 0.001). In the unadjusted Kaplan-Meier analysis, there was no significant difference in OS between NAC vs NET [5-year OS: NAC 0.935 vs NET 0.916; p = 0.08]. After adjustment for demographics, disease characteristics, and treatments, there remained no association between OS and study group (NAC vs NET; p = 0.63). CONCLUSIONS Patients with ER + /HER2- early-stage breast cancer who achieved pCR had similar OS, regardless of whether they received NAC or NET. As such, pCR appears to have similar prognostic value irrespective of the type of systemic therapy used to obtain this favorable outcome.
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Affiliation(s)
- Tori C Nierenberg
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
| | - Samantha M Thomas
- Department of Biostatistics & Bioinformatics, Duke University, Durham, NC, USA
- Duke Cancer Institute, Durham, NC, USA
| | - Ian Halliday
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
| | - Astrid Botty van den Bruele
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
- Duke Cancer Institute, Durham, NC, USA
| | - Akiko Chiba
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
- Duke Cancer Institute, Durham, NC, USA
| | - Kendra J Modell Parrish
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
- Duke Cancer Institute, Durham, NC, USA
| | - Hannah E Woriax
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
- Duke Cancer Institute, Durham, NC, USA
| | - Maggie L DiNome
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
- Duke Cancer Institute, Durham, NC, USA
| | - Kelly E Westbrook
- Duke Cancer Institute, Durham, NC, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Jennifer K Plichta
- Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.
- Duke Cancer Institute, Durham, NC, USA.
- Department of Population Health Sciences, Duke University Medical Center, Durham, NC, USA.
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Ai D, Arrey EN, Postlewait LM, Gao Y, Li X. The prevalence and clinical significance of residual occult breast cancer after neoadjuvant chemotherapy: reassessing surgical pathology in cases initially described as pathological complete response. Histopathology 2025; 86:1112-1120. [PMID: 39904575 DOI: 10.1111/his.15417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 12/30/2024] [Accepted: 01/15/2025] [Indexed: 02/06/2025]
Abstract
AIMS Evaluation of pathological complete response (pCR) [no residual invasive carcinoma in the breast (RIC) or lymph node metastases (LNM) in surgical specimens following therapy] is typically based on evaluation of one level of haematoxylin and eosin (H&E) section. Not achieving pCR is associated with worse outcomes, and additional therapy may ensue. This study of patients with triple-negative (TNBC) or human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer who underwent neoadjuvant therapy aims to assess whether occult residual disease (ORD) can be identified in deeper sections of tumour beds and lymph nodes in cases originally reported as pCR and whether ORD is associated with worse outcomes. METHODS AND RESULTS In 84 cases of pCR (2009-17) at our institution, deeper-level recuts were assessed for ORD. Oncological and survival outcomes were compared. ORD was identified in seven of 40 TNBC (17.5%; five RIC; one LMN; one RIC and LMN) and four of 44 HER2+ (9.1%; three RIC; one LMN) cases (all residual cancer burden I). Median follow-up was 46.7 months for TNBC (one local recurrence, four distant metastases and two deaths) and 86.8 months for HER2+ (no local recurrence, three distant metastases and two deaths). All recurrence and death events occurred in patients with pCR without ORD, with no recurrence events in patients with ORD. CONCLUSIONS In patients with TNBC and HER2+ breast cancer with pCR by standard pathological assessment, occult residual disease is not uncommon. Occult disease was not associated with worse oncological or survival outcomes, suggesting standard pathological assessment is sufficient to identify clinically meaningful disease.
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Affiliation(s)
- Di Ai
- Department of Pathology and Laboratory Medicine, McGovern School of Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Eliel N Arrey
- Department of Surgery, Morehouse School of Medicine, Atlanta, GA, USA
| | - Lauren M Postlewait
- Division of Surgical Oncology, Department of Surgery, Grady Memorial Hospital, Emory University, Atlanta, GA, USA
| | - Yuan Gao
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Xiaoxian Li
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
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Kim MJ, Kim HJ, Kim JY, Shin J, Park YH. Effectiveness of Adjuvant Capecitabine in Triple-Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Treatment: A Real-World Evidence Study in Korea. Clin Breast Cancer 2025; 25:e431-e439.e4. [PMID: 39909791 DOI: 10.1016/j.clbc.2024.12.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 12/30/2024] [Accepted: 12/30/2024] [Indexed: 02/07/2025]
Abstract
BACKGROUND Residual disease after neoadjuvant chemotherapy (NAC) has important role in triple negative breast cancer (TNBC). The CREATE-X study demonstrated a survival benefit from adjuvant capecitabine (adjC) in breast cancer patients, especially for TNBC populations. Because the landscape of early TNBC treatment has been changing rapidly, an optimal adjuvant strategy for real-world practice is needed. We evaluated the effectiveness of adjC in TNBC patients with residual disease after NAC. METHOD We used de-identified, anonymous data from an institutional clinical data warehouse to retrospectively analyze 934 TNBC patients who received NAC between 2017 and 2023. Among them, 405 patients received at least 1 cycle of adjC, and 77 received no adjuvant treatment. The primary outcomes of the study were distant-disease free survival (DDFS) rate and overall survival (OS) rate at 3 years. The secondary outcomes were subgroup analyses and Cox regression analyses of survival outcomes. RESULT The median follow up period was 34.3 months (range 1.8-71.5). The DDFS rate at 3 years was higher in the capecitabine group: 86.3% of the capecitabine group and 74.4% of the no adjuvant group (P = .019). The OS rates at 3 years were 93.3% and 83.8%, respectively (P = .032). Subgroup analyses indicated a greater benefit from adjC in patients aged 50 years or older and those who received platinum-based NAC, both in terms of DDFS and OS. CONCLUSION Our study showed that adjC was more effective than no adjuvant treatment for TNBC patients with residual disease in terms of DDFS and OS.
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Affiliation(s)
- Min Jeong Kim
- Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea; Research Institution for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Hyo Jung Kim
- Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea; Research Institution for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Ji-Yeon Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Junghoon Shin
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yeon Hee Park
- Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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Liu H, Kou F, Hu L, Sun J, Zhang J, Xu Y, Yao L, Xie Y. Potential candidates for adjuvant olaparib treatment in operable breast cancer patients with germline BRCA1/2 pathogenic variants after neoadjuvant chemotherapy. Breast Cancer Res Treat 2025; 211:705-715. [PMID: 40106205 DOI: 10.1007/s10549-025-07687-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 03/14/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Human epidermal growth factor receptor 2 (HER2)-negative operable breast cancer (BC) patients with germline BRCA1/2 pathogenic variants may benefit from adjuvant olaparib treatment. However, data about how many patients were eligible for olaparib treatment in operable BC patients with BRCA1/2 variants after neoadjuvant chemotherapy (NACT) is lacking. METHODS A total of 341 operable BC with germline BRCA1/2 pathogenic variants who received NACT at our institute between October 2003 and May 2015 were included. Pathological complete response (pCR) and survival were estimated. RESULTS Of the 341 BRCA1/2 carriers (BRCA1: 139; BRCA2: 202), 295 (88.1%) cases exhibited HER2-negative BC in the entire cohort. The most common subtype was triple-negative (TN) BC (62.0%) for BRCA1 carriers and hormone receptor (HR)-positive/HER2-negative BC (68.2%) for BRCA2 carriers, respectively. The pCR rate were 39.6% for BRCA1 carriers and 28.2% for BRCA2 carries. The pCR rate in TNBC, HR-positive/HER2-negative BC, and HER2-positive BC were 45.0%, 22.3%, and 45.0% in the entire cohort, respectively. Of these HR-positive/HER2-negative BC patients, 16.0% had non-pCR and exhibited CPS+EG≥3. Overall, 31.9% of the HER2-negative BC cohort were potential candidates for adjuvant olaparib, with 44.0% for BRCA1 carriers and 22.9% for BRCA2 carriers. Furthermore, patients with non-pCR exhibited a worse survival regardless of TNBC and HR-positive/HER2-negative BC disease, especially for HR-positive/HER2-negative BC with CPS+EG≥3. CONCLUSION Approximately one-third of HER2-negative BC patients with BRCA1/2 pathogenic variants are potential candidates for adjuvant olaparib treatment after NACT, with a higher proportion for BRCA1 carriers compared to BRCA2 carriers.
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Affiliation(s)
- Huimin Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Furong Kou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Comprehensive Clinical Trial Ward, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Li Hu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Jie Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Juan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Ye Xu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Lu Yao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yuntao Xie
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Comprehensive Clinical Trial Ward, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
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Perry LM, Sevilimedu V, Polidorio N, Abuhadra N, Morrow M, Plitas G, Downs-Canner S. Predictors of Pathologic Complete Response with Neoadjuvant Chemo-Immunotherapy in Early-Stage Triple-Negative Breast Cancer. Ann Surg Oncol 2025; 32:3991-4001. [PMID: 40025324 PMCID: PMC12055475 DOI: 10.1245/s10434-025-17081-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 02/07/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND The combination of pembrolizumab with neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) improves pathologic complete response (pCR) rates and event-free survival. Yet it is unclear which patients benefit most from the addition of immunotherapy. This study aims to identify predictive factors for pCR in patients with TNBC receiving chemo-immunotherapy (chemo-IO). PATIENTS AND METHODS This single-institution retrospective analysis included 283 consecutive patients with TNBC treated with neoadjuvant chemo-IO from 1 June 2021 to 20 January 2023. The primary outcome was overall pCR; secondary outcomes were breast pCR and nodal pCR. Univariate and multivariable logistic regression models assessed for characteristics associated with overall, breast, or nodal pCR. RESULTS Most patients presented with cT2 (71%) cN0 (54%) disease. The overall pCR rate was 57%, breast pCR was 58%, and axillary pCR was 67% among biopsy-proven cN+ patients. Race, pathogenic BRCA mutations, backbone chemotherapy regimen, immune-related adverse events, and disruptions in immunotherapy were not associated with pCR. Univariate associations with overall pCR were younger age (p = 0.04), lower clinical T stage (p = 0.01), ductal histology (p < 0.001), poor differentiation (p < 0.001), and unifocality (p < 0.001). Breast and axillary pCR had similar associations. Nodal pCR also had univariate associations with normal body mass index (BMI) (p = 0.04) and absence of lymphovascular invasion (LVI) (p = 0.04). On multivariable analyses, ductal histology and unifocality remained independently associated with overall and breast pCR. CONCLUSIONS This analysis showed few clinical variables to be independently associated with pCR after neoadjuvant chemo-IO for TNBC. Thus, predicting chemo-IO response to personalize treatment and minimize morbidity may instead lie in ongoing basic and translational research to assess for useful biomarkers.
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Affiliation(s)
- Lauren M Perry
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Varadan Sevilimedu
- Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Natalia Polidorio
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nour Abuhadra
- Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Monica Morrow
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - George Plitas
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Stephanie Downs-Canner
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Huang Z, Liu Y, Li S, Li Y, Wu Z, He H, Yang Y, Jin L. IHC4 and COMBINE scores for enhanced prognostic stratification in HR+/HER2- breast cancer patients after neoadjuvant chemotherapy. Breast Cancer Res Treat 2025; 211:307-319. [PMID: 39954110 PMCID: PMC12006200 DOI: 10.1007/s10549-025-07645-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Accepted: 02/10/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND The prognostic value of pathological complete response (pCR) in HR+/HER2- breast cancer patients following neoadjuvant chemotherapy (NAC) is limited, as many of these patients achieve long-term survival regardless of pCR status. The effectiveness of current tools-residual cancer burden (RCB), the Miller-Payne (MP) score, CPS-EG score and the immunohistochemical 4 (IHC4)-in this subgroup remains uncertain. In this study, we validated the prognostic role of these approaches and developed a COMBINED score capable of more accurately stratifying patients into distinct risk groups, effectively identifying low-risk patients with favorable outcomes who may be suitable for treatment de-escalation. METHODS This study retrospectively analyzed 601 HR+/HER2- breast cancer patients at Sun Yat-sen Memorial Hospital who did not achieve pCR following NAC. Patients were stratified using the IHC4, RCB, MP, CPS-EG, and a novel COMBINE score (integrating CPS-EG and IHC4). Survival outcomes, including disease-free survival (DFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis and Cox regression, with time-dependent ROC and concordance index (C-index) calculations to assess prognostic performance. RESULTS The IHC4 and CPS-EG scores outperformed the RCB and MP scores in predicting DFS and OS for non-pCR HR+/HER2- patients. The COMBINE score further enhanced prognostic accuracy, stratifying patients into four risk groups with significant differences in 5-year DFS (96.5% for low-risk vs. 55.1% for high-risk) and OS (100% for low-risk vs. 63.4% for high-risk). The COMBINE score consistently demonstrated superior AUC and C-index values compared to the CPS-EG and IHC4 scores individually at all time points (all p-values < 0.05). CONCLUSION The IHC4 score adds prognostic value beyond the CPS-EG score in HR+/HER2- breast cancer patients post-NAC. The COMBINE score, integrating both systems, offers superior prognostic stratification, highlighting the importance of combining clinical staging with tumor biology. Future studies with independent datasets are needed to validate these findings. This study provides valuable insights for optimizing treatment decisions in HR+/HER2- breast cancer.
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Affiliation(s)
- Zhenhua Huang
- Department of Breast Surgery, Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, People's Republic of China
| | - Yao Liu
- Pathology Department, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Shunyin Li
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People's Republic of China
| | - Yudong Li
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People's Republic of China
| | - Zongqi Wu
- Department of Breast Oncology and Surgery, Shenzhen Qianhai Taikang Hospital, Shenzhen, People's Republic of China
| | - Haiyan He
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People's Republic of China
| | - Yaping Yang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People's Republic of China.
| | - Liang Jin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People's Republic of China.
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Cabıoğlu N, Karanlık H, İğci A, Uras C, Dülgeroğlu O, Karadeniz Çakmak G, Sezer A, Gürleyik G, Tükenmez M, Bademler S, Müslümanoğlu M, Özkurt E, Yıldırım N, Uğurlu MÜ, Balbaloğlu H, Emiroğlu S, Özmen V, Güllüoğlu BM. Omission of axillary dissection after neoadjuvant systemic treatment in initially node-positive HER2-overexpressed and triple-negative breast cancer patients: SENATURK OTHER-NAC study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109642. [PMID: 40009910 DOI: 10.1016/j.ejso.2025.109642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 01/11/2025] [Accepted: 01/24/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND More data is needed for those patients with aggressive tumor biology with a high recurrence risk for de-escalating axillary surgery in clinically N+ breast cancer. We, therefore, investigated the outcome in cN+ patients with HER2+ or triple-negative breast cancer who were treated with sentinel lymph node biopsy alone following neoadjuvant systemic treatment. MATERIAL AND METHODS Clinically N+ patients (cT1-4N1-3M0) with HER2+ and triple-negative breast cancer at admission and downstaged to cN0 with neoadjuvant systemic treatment were included in the study. All patients were treated with sentinel node biopsy alone without further axillary dissection but followed by regional nodal irradiation. RESULTS Of 259 patients, the pathologic complete response rate was 47.1 %. Overall, 171 (66 %) patients had HER2+ and 88 (34 %) had triple-negative cancer. Of 56 ypN+ patients, the lymph node metastases were macrometastases in 24 (42.9 %) patients. After a median follow-up of 46 months, irrespective of ypN status, isolated axillary, locoregional, and distant recurrence rates were 0.8 %, 2.7 %, and 7.7 %, respectively. Recurrence and disease-specific death rates were not different between HER2+ and triple-negative cancer as well as ypN+ and ypN0 patients. Advanced cT stage (cT3-4) was the only significant factor associated with poor disease-free and disease-specific survivals. CONCLUSION Irrespective of the final ypN status and tumor subtype, omission of axillary dissection resulted with low axillary recurrence rate in initially cN+ HER2+ and triple-negative breast cancer patients who were downstaged to cN0 with neoadjuvant systemic treatment and did not receive axillary dissection.
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Affiliation(s)
- N Cabıoğlu
- Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery, Breast Unit, Istanbul, Turkiye.
| | - H Karanlık
- Istanbul University, Institute of Oncology, Department of Surgical Oncology, Istanbul, Turkiye
| | - A İğci
- Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery, Breast Unit, Istanbul, Turkiye; American Hospital, Department of Surgery, Istanbul, Turkiye
| | - C Uras
- Acibadem Mehmet Ali Aydinlar University, School of Medicine, Department of General Surgery, Istanbul, Turkiye
| | - O Dülgeroğlu
- Acibadem Mehmet Ali Aydinlar University, School of Medicine, Department of General Surgery, Istanbul, Turkiye
| | - G Karadeniz Çakmak
- Zonguldak Bülent Ecevit University, School of Medicine, Department of General Surgery, Zonguldak, Turkiye
| | - A Sezer
- Trakya University, School of Medicine, Department of General Surgery, Edirne, Turkiye
| | - G Gürleyik
- Health Sciences University, Haydarpasa Research and Training Hospital, Department of General Surgery, Istanbul, Turkiye
| | - M Tükenmez
- Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery, Breast Unit, Istanbul, Turkiye
| | - S Bademler
- Istanbul University, Institute of Oncology, Department of Surgical Oncology, Istanbul, Turkiye
| | - M Müslümanoğlu
- Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery, Breast Unit, Istanbul, Turkiye
| | - E Özkurt
- Demiroğlu Science University School of Medicine, Department of General Surgery, Istanbul, Turkiye; Istanbul Florence Nightingale Hospital, Istanbul, Turkiye
| | - N Yıldırım
- American Hospital, Department of Surgery, Istanbul, Turkiye
| | - M Ü Uğurlu
- Marmara University School of Medicine, Department of General Surgery, Istanbul, Turkiye
| | - H Balbaloğlu
- Zonguldak Bülent Ecevit University, School of Medicine, Department of General Surgery, Zonguldak, Turkiye
| | - S Emiroğlu
- Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery, Breast Unit, Istanbul, Turkiye
| | - V Özmen
- Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery, Breast Unit, Istanbul, Turkiye; Istanbul Florence Nightingale Hospital, Istanbul, Turkiye
| | - B M Güllüoğlu
- Marmara University School of Medicine, Department of General Surgery, Istanbul, Turkiye
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9
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Chen X, Ye H, Xu D, Chen S, Wu W, Qian X, Zhang X, Zou X, Chen J, Wang X. Pathological complete response and prognostic predictive factors of neoadjuvant chemoimmunotherapy in early stage triple-negative breast cancer. Front Immunol 2025; 16:1570394. [PMID: 40421023 PMCID: PMC12104239 DOI: 10.3389/fimmu.2025.1570394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 04/21/2025] [Indexed: 05/28/2025] Open
Abstract
Background Neoadjuvant chemoimmunotherapy (nCIT) has shown promise in treating early-stage triple-negative breast cancer (eTNBC), but predictive biomarkers for pathological response and prognosis remain poorly defined. Objective This study aimed to explore pathological complete response and prognostic predictive factors in eTNBC patients treated with nCIT. Materials and methods We retrospectively analyzed 112 eTNBC patients who underwent surgery after nCIT at Sun Yat-sen University Cancer Center between June 2019 and June 2023. Pathological response was assessed using Miller-Payne grade. Clinicopathological features and hematologic markers were analyzed with univariate and multivariate logistic regression or Cox regression, as well as Kaplan-Meier survival curves. Objective response rate (ORR), pathological complete response (pCR), and disease-free survival (DFS) were evaluated. Nomograms predicting pCR and DFS were constructed based on significant risk factors and the systemic inflammatory response index (SIRI). Results Higher baseline lymphocyte counts (P=0.004) were independently associated with a higher pCR rate, while elevated monocyte counts (P=0.006), neutrophil-to-lymphocyte ratio (P=0.005), platelet-to-lymphocyte ratio (p = 0.005), SIRI (P=0.037), systemic immune-inflammation index (P=0.029), and preoperative SIRI (P=0.010) were associated with a lower pCR rate. Higher baseline SIRI (P= 0.009) was correlated with shorter DFS, while higher preoperative lymphocyte counts (P=0.019) predicted longer DFS. Nomograms incorporating SIRI showed high accuracy in predicting pCR and DFS. Conclusion Hematologic inflammatory markers, particularly SIRI, are cost-effective and reliable predictors of prognosis and treatment efficacy in eTNBC patients undergoing nCIT, helping clinicians develop personalized treatment strategies. Clinical trial registration https://www.medicalresearch.org.cn/, identifier MR-44-24-046099.
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Affiliation(s)
- Xuwei Chen
- Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Hengming Ye
- Department of Disease Prevention and Control, Public Health Service Center of Bao'an District, Shenzhen, Guangdong, China
| | - Daming Xu
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Siqi Chen
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Wei Wu
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Xiaoyu Qian
- Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Xinyu Zhang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Xuxiazi Zou
- Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Junquan Chen
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Xi Wang
- Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ;China
- Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
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10
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Di Leone A, Franco A, Castagnetta V, Silenzi M, Accetta C, Carnassale B, D’Archi S, De Lauretis F, Di Guglielmo E, Gagliardi F, Magno S, Moschella F, Natale M, Sanchez AM, Scardina L, Masetti R, Franceschini G. Personalizing Neoadjuvant Chemotherapy: The Impact of BRCA Variants on Pathologic Complete Response in Luminal B Breast Cancer. Cancers (Basel) 2025; 17:1619. [PMID: 40427118 PMCID: PMC12110214 DOI: 10.3390/cancers17101619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Revised: 04/29/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Neoadjuvant chemotherapy (NACT) is effective in downstaging locally advanced breast cancer, improving surgical and oncological outcomes. However, luminal B breast cancer typically exhibits a poorer response to NACT, with only 10-15% of patients achieving a pathologic complete response (pCR). This study investigates whether BRCA pathogenic variants (BRCA PVs) influence pCR rates in luminal B breast cancer patients, aiming to identify potential predictors for personalized treatment strategies. Materials and Methods: This retrospective study included luminal B breast cancer patients who underwent NACT at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2014 and June 2023. Patients were stratified according to BRCA status: BRCA PVs and BRCA wild-type (WT). Primary endpoint was to evaluate pCR rates, while secondary endpoints included locoregional disease-free survival (LR-DFS), distant disease-free survival (DDFS), and overall survival (OS). Results: In total, 495 patients were enrolled, of whom 442 (89.3%) carried BRCA WT and 53 (10.7%) BRCA PVs. The pCR rate was significantly higher in the BRCA PVs group (20.8% PVs vs. 10.9% WT; p = 0.044). Specifically, the breast pCR rate was 28.3% in BRCA PVs versus 15.4% in BRCA WT (p = 0.030). BRCA WT patients had better 5-year LR-DFS (91.1% WT vs. 79.5% PVs; p = 0.003), while no significant differences were observed in 5-year DDFS or OS. Conclusions: BRCA PVs are associated with a higher pCR rate in luminal B breast cancer patients receiving NACT, suggesting a potential predictive role in tailoring treatment strategies.
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Affiliation(s)
| | | | - Virginia Castagnetta
- Multidisciplinary Breast Center, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (A.D.L.); (A.F.); (M.S.); (C.A.); (B.C.); (S.D.); (F.D.L.); (E.D.G.); (F.G.); (S.M.); (F.M.); (M.N.); (A.M.S.); (L.S.); (R.M.); (G.F.)
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11
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Wang X, Huang Y, Shi J, Cao Y, Chen H, Li L, Wang L, Tang S, Gong X, Huang H, Yin T, Zhang J. Biomechanical parameters quantified by MR elastography for predicting response to neoadjuvant chemotherapy and disease-free survival in breast cancer: a prospective longitudinal study. Breast Cancer Res 2025; 27:72. [PMID: 40329402 PMCID: PMC12057177 DOI: 10.1186/s13058-025-02035-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 04/24/2025] [Indexed: 05/08/2025] Open
Abstract
BACKGROUND Little is known regarding biomechanical properties derived from multifrequency MR elastography temporal changes during neoadjuvant chemotherapy (NAC) and associated with pathologic complete response (pCR) and disease-free survival (DFS) in breast cancer. We aimed to investigate temporal changes in NAC-associated biomechanical parameters and assess biomechanical parameters as a predictor of pCR and DFS in breast cancer. METHODS In this prospective longitudinal study, participants with breast cancer who received NAC were enrolled from February 2021 to May 2023. All participants underwent multifrequency MR-elastography at four timepoints: before NAC (T1) and after 2 (T2), 4 (T3), and 6 (T4) cycles. Tomoelastography postprocessing provided biomechanical maps of shear-wave-speed (c) and loss-angle (φ) as proxies of stiffness and viscosity. The biomechanical parameters were validated by means of correlation with histopathologic measurements. Generalized estimating equations were used to compare temporal changes in biomechanical parameters at four time points. Logistic regression was used for pCR analysis and Cox proportional hazards regression was used for survival analysis. Predictive performance was assessed with area under the receiver operating characteristic curve (AUC) analysis. RESULTS A total of 235 women (50.6 ± 7.9 years) with 964 scans were enrolled. Biomechanical parameters were supported by positive correlations with pathologic examination-based stroma fraction (c: r =.76, P <.001; φ: r =.49, P =.008) and cellularity (c: r =.58, P =.001; φ: r =.40, P =.035). Progesterone receptor, human epidermal growth factor receptor-2 (HER2), T2-c, and T2-φ were independently associated with pCR (all P <.05). Estrogen receptor, HER2, clinical stage, and change in φ at the early stage of NAC were associated with PFS (all P <.05). The predictive model, which incorporated biomechanical parameters and clinicopathologic characteristics significantly outperformed the clinicopathologic model in predicting pCR (AUC: 0.95, 95% confidence interval [CI]: 0.92, 0.98 vs. 0.79, 95%CI: 0.73, 0.84; P <.001). The predictive model also showed good discrimination ability for DFS (C-index = 0.82, 95%CI: 0.72, 0.90) and stratified prognosis into low-risk and high-risk groups (log-rank, P <.001). CONCLUSIONS During NAC, patients with higher tumor stiffness and viscosity are less likely to achieve DFS and pCR. The biomechanical parameters exhibit excellent biological interpretability and serve as valuable biomarkers for predicting pCR and DFS in patients with breast cancer.
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Affiliation(s)
- Xiaoxia Wang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Yao Huang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Jinfang Shi
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Ying Cao
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Huifang Chen
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Lan Li
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Lu Wang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Sun Tang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Xueqin Gong
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Haiping Huang
- Department of Pathology, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Ting Yin
- MR Collaborations, Siemens Healthineers Ltd, Chengdu, China
| | - Jiuquan Zhang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing, 400030, China.
- Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing University Cancer Hospital, No.181 Hanyu road, Shapingba district, Chongqing, 400030, China.
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Kuemmel S, Graeser M, Schmid P, Reinisch M, Feuerhake F, Volk V, Armeanu-Ebinger S, Schütz L, Kelemen O, Schroeder C, Ossowski S, Jóźwiak K, Kostara A, Scheffen I, Lüdtke-Heckenkamp K, Hilpert F, Kentsch A, Ziske C, Depenbusch R, Braun M, Blohmer JU, Zu Eulenburg C, Christgen M, Bartels S, Kreipe HH, Wuerstlein R, Biehl C, Pelz E, Hartkopf A, Harbeck N, Gluz O. Chemotherapy-free neoadjuvant pembrolizumab combined with trastuzumab and pertuzumab in HER2-enriched early breast cancer (WSG-KEYRICHED-1): a single-arm, phase 2 trial. Lancet Oncol 2025; 26:629-640. [PMID: 40318646 DOI: 10.1016/s1470-2045(25)00097-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 02/06/2025] [Accepted: 02/18/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Accumulating evidence indicates that about 30-40% of patients with HER2-positive early breast cancer might achieve excellent outcomes without chemotherapy. Therefore, we aimed to test the pathological complete response after the addition of pembrolizumab to dual anti-HER2 blockade and omission of chemotherapy in patients with HER2-enriched breast cancer. METHODS WSG-KEYRICHED-1 was a single-arm, multicentre, open-label, hypothesis-generating phase 2 trial done at 15 breast cancer centres in Germany. Women aged 18 years and older, with previously untreated clinical stage T1c-T3, N0-N2, M0, primary unilateral early invasive breast cancer, and locally confirmed HER2 immunohistochemistry score 2+ or 3+ status, and hormone receptor-positive or receptor-negative status, were enrolled. Women with centrally confirmed HER2-enriched subtype by prediction analysis of microarrays 50 gene set (PAM50) and an Eastern Cooperative Oncology Group performance status of 0-1 were allocated to four cycles of intravenous pembrolizumab (200 mg every 3 weeks for 12 weeks), intravenous trastuzumab biosimilar ABP 980 (8 mg/kg loading dose, then 6 mg/kg every 3 weeks for 12 weeks), and intravenous pertuzumab (840 mg loading dose, then 420 mg every 3 weeks for 12 weeks). The primary outcome was the proportion of patients with a pathological complete response (defined as ypN0 or ypT0/is), assessed in the full analysis set, which included all patients who had at least one dose of trial treatment and had central tumour assessment within 3 weeks after the end of trial treatment. For the primary endpoint to be met, at least 52·2% of patients had to have a pathological complete response to support the hypothesis that the proportion of patients with pathological complete response after trial treatment would be higher than 40% with statistical significance. Safety was analysed in all patients who had at least one dose of trial treatment. The study is registered with ClinicalTrials.gov, NCT03988036, and has been completed. FINDINGS Between Sept 2, 2020, and May 5, 2021, 48 women were enrolled, of whom four did not have surgery, and one had only a local pathological complete response assessment. Therefore, 43 patients with central pathological complete response assessment were included in the full analysis set. Median follow-up was 8·6 months (IQR 8·3-9·0). 20 (47%) of 43 patients had a pathological complete response by central assessment (lower bound of the one-sided 95% CI 33%), thus the null hypothesis (40% pathological complete response) could not be rejected (p=0·22). Four (8%) of 48 patients had grade 3-4 adverse events deemed related to drug treatment. The most common grade 3-4 adverse events were increased alanine aminotransferase (n=1), drug hypersensitivity (n=1), nephritis (n=1), and panic attack (n=1). Serious adverse events occurred in four (8%) of 48 patients, which were drug hypersensitivity (n=1), panic attack (n=1), pyrexia (n=1), and COVID-19 (n=1). Pembrolizumab was discontinued or postponed due to adverse events in three (6%) of 48 patients. No deaths occurred. INTERPRETATION Although the null hypothesis could not be rejected, the WSG-KEYRICHED-1 trial highlights the potential of a short chemotherapy-free combination of pembrolizumab with dual anti-HER2 therapy, warranting the initiation of randomised trials investigating the immunotherapy without chemotherapy in patients with HER2-enriched breast cancer. FUNDING Merck Sharp & Dohme and NanoString Technologies.
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Affiliation(s)
- Sherko Kuemmel
- West German Study Group, Moenchengladbach, Germany; Breast Unit, Clinics Essen-Mitte, Essen, Germany; Department of Gynecology with Breast Center, Charité-University Medicine Berlin, Berlin, Germany.
| | - Monika Graeser
- West German Study Group, Moenchengladbach, Germany; Breast Center Niederrhein, Ev Hospital Bethesda, Moenchengladbach, Germany; Department of Obstetrics and Gynecology, University Witten-Herdecke, Witten, Germany
| | | | - Mattea Reinisch
- Breast Unit, Clinics Essen-Mitte, Essen, Germany; Department of Gynecology with Breast Center, Charité-University Medicine Berlin, Berlin, Germany
| | - Friedrich Feuerhake
- Institute of Pathology, Hannover Medical School, Hannover, Germany; Institute of Neuropathology, University Clinic Freiburg, Freiburg, Germany
| | - Valery Volk
- Institute of Pathology, Hannover Medical School, Hannover, Germany
| | - Sorin Armeanu-Ebinger
- Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
| | - Leon Schütz
- Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
| | - Olga Kelemen
- Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
| | - Christopher Schroeder
- Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
| | - Stephan Ossowski
- Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
| | - Katarzyna Jóźwiak
- Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany
| | | | - Iris Scheffen
- West German Study Group, Moenchengladbach, Germany; Breast Center Niederrhein, Ev Hospital Bethesda, Moenchengladbach, Germany
| | | | - Felix Hilpert
- Breast Center Hamburg, Hospital Jerusalem, Hamburg, Germany
| | - Angela Kentsch
- Department of Gynecology, Diakovere Henriettenstift, Hanover, Germany
| | - Carsten Ziske
- Internal Medicine, St Josef-Hospital, GFO Kliniken Troisdorf, Troisdorf, Germany
| | | | - Michael Braun
- Breast Center, Rotkreuz Clinics Munich, Munich, Germany
| | - Jens Uwe Blohmer
- Department of Gynecology with Breast Center, Charité-University Medicine Berlin, Berlin, Germany
| | - Christine Zu Eulenburg
- West German Study Group, Moenchengladbach, Germany; Department of Medical Biometry and Epidemiology, University Medical Center Hamburg, Hamburg, Germany
| | | | - Stephan Bartels
- Institute of Pathology, Hannover Medical School, Hannover, Germany
| | | | - Rachel Wuerstlein
- West German Study Group, Moenchengladbach, Germany; Breast Center, Department of Gynecology and Obstetrics and CCCMunich, LMU University Hospital Munich, BZKF, Munich, Germany
| | - Claudia Biehl
- Department of Gynecology, Klinikum Dortmund gGmbH, Dortmund, Germany; University Hospital Witten-Herdecke, Witten, Germany
| | | | - Andreas Hartkopf
- Department of Women's Health, University Hospital Tübingen, Tübingen, Germany
| | - Nadia Harbeck
- West German Study Group, Moenchengladbach, Germany; Breast Center, Department of Gynecology and Obstetrics and CCCMunich, LMU University Hospital Munich, BZKF, Munich, Germany
| | - Oleg Gluz
- West German Study Group, Moenchengladbach, Germany; Breast Center Niederrhein, Ev Hospital Bethesda, Moenchengladbach, Germany; University Clinics Cologne, Cologne, Germany
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Mousa-Doust D, Bazzarelli A, Deban M, Dingee C, Newman-Bremang J, Pao JS, Warburton R, McKevitt E. Inflammatory breast cancer response to modern neoadjuvant chemotherapy: Tumor response and survival outcomes. Am J Surg 2025; 243:116288. [PMID: 40088610 DOI: 10.1016/j.amjsurg.2025.116288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 01/22/2025] [Accepted: 03/03/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer. This study evaluates oncologic outcomes in IBC patients treated with modern multimodal treatment. METHODS A retrospective review analyzed clinicopathologic data of 5063 patients, 646 of whom underwent NAC followed by surgery between 2012 and 2024. Survival outcomes were compared across biologic subtypes. RESULTS Twenty-six cases of T4dM0 IBC were identified, with 57.7 % HER-2 positive, 26.9 % ER positive/HER-2 negative, and 15.4 % ER negative/HER-2 negative. The total pCR rate was highest in HER-2 positive (53.3 %) and lowest in ER-positive/HER-2 negative patients (p = 0.036). Among 19 patients with ≥3 years of follow-up, 47 % experienced recurrence (78 % distant and 22 % locoregional) and 42 % died of breast cancer. No significant differences in locoregional recurrence, or survival outcomes were found across subtypes. CONCLUSION pCR has limited prognostic value in IBC. Although HER-2 positive patients are more likely to achieve pCR, this does not necessarily translate into improved outcomes.
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Affiliation(s)
- Dorsa Mousa-Doust
- Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC, V5Z 1M9, Canada.
| | - Amy Bazzarelli
- Providence Breast Centre, Mount Saint Joseph Hospital, 3080 Prince Edward Street, Vancouver, BC, V5T 3N4, Canada; Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC, V5Z 1M9, Canada.
| | | | - Carol Dingee
- Providence Breast Centre, Mount Saint Joseph Hospital, 3080 Prince Edward Street, Vancouver, BC, V5T 3N4, Canada; Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC, V5Z 1M9, Canada.
| | - Jieun Newman-Bremang
- Providence Breast Centre, Mount Saint Joseph Hospital, 3080 Prince Edward Street, Vancouver, BC, V5T 3N4, Canada; Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC, V5Z 1M9, Canada.
| | - Jin-Si Pao
- Providence Breast Centre, Mount Saint Joseph Hospital, 3080 Prince Edward Street, Vancouver, BC, V5T 3N4, Canada; Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC, V5Z 1M9, Canada.
| | - Rebecca Warburton
- Providence Breast Centre, Mount Saint Joseph Hospital, 3080 Prince Edward Street, Vancouver, BC, V5T 3N4, Canada; Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC, V5Z 1M9, Canada.
| | - Elaine McKevitt
- Providence Breast Centre, Mount Saint Joseph Hospital, 3080 Prince Edward Street, Vancouver, BC, V5T 3N4, Canada; Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC, V5Z 1M9, Canada.
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Pesapane F, Rotili A, Scalco E, Pupo D, Carriero S, Corso F, De Marco P, Origgi D, Nicosia L, Ferrari F, Penco S, Pizzamiglio M, Rizzo G, Cassano E. Predictive value of tumoral and peritumoral radiomic features in neoadjuvant chemotherapy response for breast cancer: a retrospective study. LA RADIOLOGIA MEDICA 2025; 130:598-612. [PMID: 39992329 DOI: 10.1007/s11547-025-01969-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 02/05/2025] [Indexed: 02/25/2025]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NACT) improves surgical outcomes for breast cancer patients, with pathologic complete response (pCR) correlated with enhanced survival. The role of radiomics, particularly from peritumoral tissue, in predicting pCR remains under investigation. METHODS This retrospective study analyzed radiomic features from pretreatment dynamic contrast-enhanced breast MRI scans of 150 patients undergoing NACT. A proportional approach was used to define peritumoral zones, assessed both with a 10% and 30% extension, allowing more standardized assessments relative to the tumor size. Radiomic features were evaluated alongside clinical and biological data to predict pCR. The association of clinical/biological and radiomic features with pCR to NACT was evaluated using univariate and multivariate analysis, logistic regression, and a random forest model. A clinical/biological model, a radiomic model, and a combined clinical/biological and 4 radiomic models for predicting the response to NACT were constructed. Area under the curve (AUC) and 95% confidence intervals (CIs) were used to assess the performance of the models. RESULTS Ninety-five patients (average age 47 years) were finally included. HER2 + , basal-like molecular subtypes, and a high level of Ki67 (≥ 20%) were associated with a higher likelihood of pCR to NACT. The combined clinical-biological-radiomic model, especially with a 10% peritumoral extension, showed improved predictive accuracy (AUC 0.76, CI 0.65-0.85) compared to models using clinical-biological data alone (AUC 0.73, CI 0.63-0.83). CONCLUSIONS Integrating peritumoral radiomic features with clinical and biological data enhances the prediction of pCR to NACT, underscoring the potential of a multifaceted approach in treatment personalization.
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Affiliation(s)
- Filippo Pesapane
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy.
| | - Anna Rotili
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Elisa Scalco
- Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche (ITB-CNR), Segrate, MI, Italy
| | - Davide Pupo
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Serena Carriero
- Department of Radiology and Interventional Radiology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Federica Corso
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Paolo De Marco
- Medical Physics Unit, European Institute of Oncology, IRCCS, Milan, Italy
| | - Daniela Origgi
- Medical Physics Unit, European Institute of Oncology, IRCCS, Milan, Italy
| | - Luca Nicosia
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Federica Ferrari
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Silvia Penco
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Maria Pizzamiglio
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Giovanna Rizzo
- Istituto di Sistemi e Tecnologie Industriali Intelligenti per il Manifatturiero Avanzato (STIIMA), CNR, Segrate, MI, Italy
| | - Enrico Cassano
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
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Ferezini Oliveira de Sá G, Villarim PVDO, Saboia da Escossia Melo PH, Sarmento ACA, Gonçalves AK, Santos de Medeiros K, Rocha de Medeiros Miranda C. Evaluation of pathological complete response rates in breast cancer patients undergoing neoadjuvant therapy. REVISTA BRASILEIRA DE GINECOLOGIA E OBSTETRÍCIA 2025; 47:e-rbgo13. [PMID: 40406477 PMCID: PMC12097449 DOI: 10.61622/rbgo/2025rbgo13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/27/2024] [Indexed: 05/26/2025] Open
Abstract
Objective This study aims to assess the rate of pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant therapy and to explore its correlation with clinical, molecular, and prognostic factors. Methods We conducted this retrospective observational study at Liga Contra o Câncer, a major public oncology reference center in Northeast Brazil. We included patients diagnosed with breast cancer who initiated neoadjuvant therapy between June 2018 and June 2019. Patients with a history of recurrent breast cancer or those who did not undergo surgery were excluded. The primary outcome was the pCR rate, with secondary outcomes including Overall Survival (OS), Disease-Free Survival (DFS), mortality, and disease recurrence. Follow-up extended until August 2022. We performed multivariate Cox regression analysis to correlate outcomes with predetermined variables. Results Of the 292 included patients, 63 (21.6%) achieved pCR. The mean follow-up duration was 42.8 months. Multivariate logistic regression analysis revealed an association between pCR and the AC-TH regimen [OR = 2.4; 95%CI = 1.13 - 5.24; p=0.023], as well as between pCR and HER2-positive tumors [OR 2.49; 95% CI = 1.14 - 5.86; p=0.028]. Complete pathological response was associated with higher DFS [HR 0.33; 95%CI 0.13-0.86; p=0.024]. Conclusion Neoadjuvant therapy demonstrated significant efficacy in achieving pathological response in breast cancer patients. We observed a strong association between the AC-TH regimen, HER2-positive status, and pCR.
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Affiliation(s)
| | | | | | - Ayane Cristine Alves Sarmento
- Universidade Federal do Rio Grande do NorteNatalRNBrazilUniversidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
- Liga Contra o CâncerNataRNBrazilLiga Contra o Câncer, Nata, RN, Brazil.
| | - Ana Katherine Gonçalves
- Universidade Federal do Rio Grande do NorteNatalRNBrazilUniversidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
| | - Kleyton Santos de Medeiros
- Universidade Federal do Rio Grande do NorteNatalRNBrazilUniversidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
- Liga Contra o CâncerNataRNBrazilLiga Contra o Câncer, Nata, RN, Brazil.
| | - Cristina Rocha de Medeiros Miranda
- Universidade Federal do Rio Grande do NorteNatalRNBrazilUniversidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
- Liga Contra o CâncerNataRNBrazilLiga Contra o Câncer, Nata, RN, Brazil.
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16
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Kivuyo N, Akoko L, Mutajwaha JOG, Haule C, Mosha I, Misidai M, Kitua D, Nyongole O, Mwanga A. Dismal pathological response to neoadjuvant chemotherapy in stage III breast cancer patients in Tanzania: A retrospective review. PLoS One 2025; 20:e0321187. [PMID: 40267089 PMCID: PMC12017560 DOI: 10.1371/journal.pone.0321187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 03/03/2025] [Indexed: 04/25/2025] Open
Abstract
Response to neoadjuvant treatment in breast cancer has been associated with good oncological outcomes. In Tanzania, a majority of breast cancer patients are diagnosed at stage III; hence, they almost always require neoadjuvant therapy. However, the response to neoadjuvant therapy in these patients remains unknown. This study examined the pathological responses in women with stage III breast cancer who underwent neoadjuvant therapy and identified sociodemographic and clinical predictors of the pathological response in this cohort. This hospital-based retrospective cohort study was conducted between December 2021 and April 2022. It included women with breast cancer who received neoadjuvant therapy and underwent surgery for breast cancer at Muhimbili National Hospital in Tanzania, from January 2018 through December 2021. Data analysis was performed using SPSS version 25. A complete pathological response was identified upon pathological review of the mastectomy specimen. Chi-square tests and Fischer's exact tests were used to evaluate the factors associated with a complete pathological response, with a p value of less than 0.05 indicating statistical significance. Ethical approval was obtained from the Muhimbili University of Health and Allied Sciences Institutional Review Board. The study complied with the Helsinki Declaration on studies involving human subjects. A total of 181 breast cancer patients were recruited for the study, with a mean age of 51±12.6 (28-89) years. A complete pathological response to neoadjuvant therapy was observed in 40 (22.1%) patients which is relatively lower compared to studies from Western countries. Disease stage at diagnosis was associated with response to neoadjuvant therapy, with those at stage IIIA showing better complete response than those at stages IIIB and IIIC indicating a need to improve diagnostic strategies to capture patients in the earlier stages to improve outcomes.
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Affiliation(s)
- Nashivai Kivuyo
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Larry Akoko
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - John of God Mutajwaha
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Caspar Haule
- Department of Surgery, Muhimbili National Hospital, Dar es Salaam, Tanzania
| | - Innocent Mosha
- Department of Pathology, Muhimbili National Hospital, Dar-es-Salaam, Tanzania
| | - Mungeni Misidai
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Daniel Kitua
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Obadia Nyongole
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Ally Mwanga
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
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17
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Toney NJ, Lynch MT, Lynce F, Mainor C, Isaacs C, Schlom J, Donahue RN. Serum analytes as predictors of disease recurrence and the duration of invasive disease-free survival in patients with triple negative breast cancer enrolled in the OXEL trial treated with immunotherapy, chemotherapy, or chemoimmunotherapy. J Immunother Cancer 2025; 13:e011379. [PMID: 40274284 PMCID: PMC12020768 DOI: 10.1136/jitc-2024-011379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND The OXEL study (NCT03487666) was a phase II trial of patients with triple negative breast cancer (TNBC) with residual disease following neoadjuvant chemotherapy, randomized to receive immunotherapy (anti-programmed cell death protein 1, nivolumab), chemotherapy (capecitabine), or chemoimmunotherapy. We previously reported on the primary endpoint of the OXEL trial, demonstrating that a peripheral immunoscore based on circulating immune cells reflecting immune activation was increased in patients treated with immunotherapy. However, compared with cell-based immune assays, sera assays are more cost-effective, less labor-intensive, and samples easier to obtain. Here, we report on differences in serum analytes between treatment arms and associations with clinical response. METHODS Patients (n=38) were assayed for 97 serum analytes before and after 6 and 12 weeks of therapy. Serum analytes were assessed for changes with therapy, and as predictors of disease recurrence and the duration of invasive disease-free survival (iDFS) in both single analyte analyses and machine learning models. RESULTS Levels of specific analytes at baseline and changes in levels at early time points on treatment preceding recurrence were associated with eventual development of disease recurrence and/or the duration of iDFS. These associations varied based on the therapy patients received. Immunotherapy led to enrichment in pro-inflammatory analytes following treatment, whereas chemotherapy resulted in overall decreases. Changes seen in patients receiving chemoimmunotherapy more closely resembled those observed in patients receiving immunotherapy alone as opposed to chemotherapy alone. Furthermore, logistic regression and Cox proportional hazard models, developed using machine learning methods, demonstrated that combinations of serum analytes were more predictive of disease recurrence and iDFS duration than analyses of single serum analytes. Notably, the multivariable models that predicted patient outcomes were highly specific to the class of treatment patients received. CONCLUSIONS In patients with TNBC with residual disease after neoadjuvant chemotherapy, treatment with immunotherapy alone or chemoimmunotherapy resulted in enhanced immune activation compared with chemotherapy alone as measured by changes in serum analyte levels. Distinct serum analytes, both at baseline and as changes after therapy, predicted clinical outcomes for patients receiving immunotherapy alone, chemotherapy alone, or chemoimmunotherapy. TRIAL REGISTRATION NUMBER NCT03487666.
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Affiliation(s)
- Nicole J Toney
- Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Megan T Lynch
- Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Filipa Lynce
- Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Candace Mainor
- MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Claudine Isaacs
- Georgetown University, Washington, District of Columbia, USA
| | - Jeffrey Schlom
- Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Renee N Donahue
- Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
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18
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Luo L, Wu M, Li M, Xin Y, Wang Q, Vardhanabhuti V, Chu WC, Li Z, Zhou J, Rajpurkar P, Chen H. A large model for non-invasive and personalized management of breast cancer from multiparametric MRI. Nat Commun 2025; 16:3647. [PMID: 40246826 PMCID: PMC12006510 DOI: 10.1038/s41467-025-58798-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 04/02/2025] [Indexed: 04/19/2025] Open
Abstract
Breast Magnetic Resonance Imaging (MRI) demonstrates the highest sensitivity for breast cancer detection among imaging modalities and is standard practice for high-risk women. Interpreting the multi-sequence MRI is time-consuming and prone to subjective variation. We develop a large mixture-of-modality-experts model (MOME) that integrates multiparametric MRI information within a unified structure, leveraging breast MRI scans from 5205 female patients in China for model development and validation. MOME matches four senior radiologists' performance in identifying breast cancer and outperforms a junior radiologist. The model is able to reduce unnecessary biopsies in Breast Imaging-Reporting and Data System (BI-RADS) 4 patients, classify triple-negative breast cancer, and predict pathological complete response to neoadjuvant chemotherapy. MOME further supports inference with missing modalities and provides decision explanations by highlighting lesions and measuring modality contributions. To summarize, MOME exemplifies an accurate and robust multimodal model for noninvasive, personalized management of breast cancer patients via multiparametric MRI.
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Affiliation(s)
- Luyang Luo
- Department of Computer Science and Technology, The Hong Kong University of Science and Technology, Hong Kong, China
- Department of Biomedical Informatics, Harvard University, Boston, USA
| | - Mingxiang Wu
- Department of Radiology, Shenzhen People's Hospital, Shenzhen, China
| | - Mei Li
- Department of Radiology, PLA Middle Military Command General Hospital, Wuhan, China
| | - Yi Xin
- Department of Computer Science and Technology, The Hong Kong University of Science and Technology, Hong Kong, China
| | - Qiong Wang
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Varut Vardhanabhuti
- Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Winnie Cw Chu
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong, China
| | - Zhenhui Li
- Department of Radiology, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China.
| | - Juan Zhou
- Department of Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, China.
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
| | - Pranav Rajpurkar
- Department of Biomedical Informatics, Harvard University, Boston, USA
| | - Hao Chen
- Department of Computer Science and Technology, The Hong Kong University of Science and Technology, Hong Kong, China.
- Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.
- State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
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19
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Jin Y, Zhao M, Su T, Fan Y, Ouyang Z, Lv F. Comparing Random Survival Forests and Cox Regression for Nonresponders to Neoadjuvant Chemotherapy Among Patients With Breast Cancer: Multicenter Retrospective Cohort Study. J Med Internet Res 2025; 27:e69864. [PMID: 40198909 PMCID: PMC12015342 DOI: 10.2196/69864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 02/19/2025] [Accepted: 03/25/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Breast cancer is one of the most common malignancies among women worldwide. Patients who do not achieve a pathological complete response (pCR) or a clinical complete response (cCR) post-neoadjuvant chemotherapy (NAC) typically have a worse prognosis compared to those who do achieve these responses. OBJECTIVE This study aimed to develop and validate a random survival forest (RSF) model to predict survival risk in patients with breast cancer who do not achieve a pCR or cCR post-NAC. METHODS We analyzed patients with no pCR/cCR post-NAC treated at the First Affiliated Hospital of Chongqing Medical University from January 2019 to 2023, with external validation in Duke University and Surveillance, Epidemiology, and End Results (SEER) cohorts. RSF and Cox regression models were compared using the time-dependent area under the curve (AUC), the concordance index (C-index), and risk stratification. RESULTS The study cohort included 306 patients with breast cancer, with most aged 40-60 years (204/306, 66.7%). The majority had invasive ductal carcinoma (290/306, 94.8%), with estrogen receptor (ER)+ (182/306, 59.5%), progesterone receptor (PR)- (179/306, 58.5%), and human epidermal growth factor receptor 2 (HER2)+ (94/306, 30.7%) profiles. Most patients presented with T2 (185/306, 60.5%), N1 (142/306, 46.4%), and M0 (295/306, 96.4%) staging (TNM meaning "tumor, node, metastasis"), with 17.6% (54/306) experiencing disease progression during a median follow-up of 25.9 months (IQR 17.2-36.3). External validation using Duke (N=94) and SEER (N=2760) cohorts confirmed consistent patterns in age (40-60 years: 59/94, 63%, vs 1480/2760, 53.6%), HER2+ rates (26/94, 28%, vs 935/2760, 33.9%), and invasive ductal carcinoma prevalence (89/94, 95%, vs 2506/2760, 90.8%). In the internal cohort, the RSF achieved significantly higher time-dependent AUCs compared to Cox regression at 1-year (0.811 vs 0.763), 3-year (0.834 vs 0.783), and 5-year (0.810 vs 0.771) intervals (overall C-index: 0.803, 95% CI 0.747-0.859, vs 0.736, 95% CI 0.673-0.799). External validation confirmed robust generalizability: the Duke cohort showed 1-, 3-, and 5-year AUCs of 0.912, 0.803, and 0.776, respectively, while the SEER cohort maintained consistent performance with AUCs of 0.771, 0.729, and 0.702, respectively. Risk stratification using the RSF identified 25.8% (79/306) high-risk patients and a significantly reduced survival time (P<.001). Notably, the RSF maintained improved net benefits across decision thresholds in decision curve analysis (DCA); similar results were observed in external studies. The RSF model also showed promising performance across different molecular subtypes in all datasets. Based on the RSF predicted scores, patients were stratified into high- and low-risk groups, with notably poorer survival outcomes observed in the high-risk group compared to the low-risk group. CONCLUSIONS The RSF model, based solely on clinicopathological variables, provides a promising tool for identifying high-risk patients with breast cancer post-NAC. This approach may facilitate personalized treatment strategies and improve patient management in clinical practice.
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Affiliation(s)
- Yudi Jin
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Zhao
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tong Su
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yanjia Fan
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zubin Ouyang
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fajin Lv
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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20
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Wu C, Lima EABF, Stowers CE, Xu Z, Yam C, Son JB, Ma J, Rauch GM, Yankeelov TE. MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens. NPJ Digit Med 2025; 8:195. [PMID: 40195521 PMCID: PMC11976917 DOI: 10.1038/s41746-025-01579-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 03/20/2025] [Indexed: 04/09/2025] Open
Abstract
We developed a practical framework to construct digital twins for predicting and optimizing triple-negative breast cancer (TNBC) response to neoadjuvant chemotherapy (NAC). This study employed 105 TNBC patients from the ARTEMIS trial (NCT02276443, registered on 10/21/2014) who received Adriamycin/Cytoxan (A/C)-Taxol (T). Digital twins were established by calibrating a biology-based mathematical model to patient-specific MRI data, which accurately predicted pathological complete response (pCR) with an AUC of 0.82. We then used each patient's twin to theoretically optimize outcome by identifying their optimal A/C-T schedule from 128 options. The patient-specifically optimized treatment yielded a significant improvement in pCR rate of 20.95-24.76%. Retrospective validation was conducted by virtually treating the twins with AC-T schedules from historical trials and obtaining identical observations on outcomes: bi-weekly A/C-T outperforms tri-weekly A/C-T, and weekly/bi-weekly T outperforms tri-weekly T. This proof-of-principle study demonstrates that our digital twin framework provides a practical methodology to identify patient-specific TNBC treatment schedules.
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Affiliation(s)
- Chengyue Wu
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Institute for Data Science in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA.
| | - Ernesto A B F Lima
- Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA
- Texas Advanced Computing Center, The University of Texas at Austin, Austin, TX, USA
| | - Casey E Stowers
- Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA
| | - Zhan Xu
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Clinton Yam
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jong Bum Son
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jingfei Ma
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gaiane M Rauch
- Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thomas E Yankeelov
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA
- Livestrong Cancer Institutes, The University of Texas at Austin, Austin, TX, USA
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA
- Department of Diagnostic Medicine, The University of Texas at Austin, Austin, TX, USA
- Department of Oncology, The University of Texas at Austin, Austin, TX, USA
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21
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Kumar U, Mishra AK, Singh KR, Parihar A, Raja N, Raam M, Rahalkar A, Ramakant P. Does Mammography Density Change the Response to Neoadjuvant Chemotherapy and Predict a Pathological Complete Response Rate? World J Surg 2025; 49:780-788. [PMID: 39988559 DOI: 10.1002/wjs.12502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 01/07/2025] [Accepted: 01/20/2025] [Indexed: 02/25/2025]
Abstract
BACKGROUND Pathological complete response (PCR) is the surrogate marker of the outcome of a breast cancer patient. Breast cancer (BC) patients have variable responses to neoadjuvant chemotherapy (NACT). The effect of chemotherapy on mammographic density (MD) is unclear in the literature. Also, MD and PCR correlation is not extensively studied. The aim of the present study is to find MD's potential as a PCR predictor in a resource-constrained setting. METHODS The study included all patients of BC-related surgery from January 2018 to June 2021 with follow-up till June 2023. MD was classified by the American College of Radiology (ACR) (classes A-D) based on breast composition. The chi-square test and logistic regression analysis were used to calculate p-values. RESULTS Out of 557 patients, 554 were female with a mean age 46.8 years (premenopausal 54.5%). ACR grades of MD A, B, C, and D were 18.1% (n = 101), 56% (n = 312), 21.5% (n = 120), and 4.3% (n = 24), respectively. The odds of having PCR with MD B, C, and D were 0.51, 0.04, and 0.03, respectively, with respect to MD A. There was a significant inverse association of PCR and Ki-67 with MD on multivariate analysis. HER2 positive, TNBC, Ki 67 > 15%, and grade 3 had significantly high PCR. CONCLUSION MD had an inverse correlation with PCR and Ki-67. Low MD, HER2 positive, TNBC, high Ki-67 subtypes, and grade 3 were good predictors for PCR.
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Affiliation(s)
- Upander Kumar
- Department of Endocrine Surgery, King George's Medical University, Lucknow, India
| | - Anand Kumar Mishra
- Department of Endocrine Surgery, King George's Medical University, Lucknow, India
| | - Kul Ranjan Singh
- Department of Endocrine Surgery, King George's Medical University, Lucknow, India
| | - Anit Parihar
- Department of Radiodiagnosis, King George's Medical University, Lucknow, India
| | - Nancy Raja
- Department of Endocrine Surgery, King George's Medical University, Lucknow, India
| | - Mithun Raam
- Department of Endocrine Surgery, King George's Medical University, Lucknow, India
| | - Ashwinee Rahalkar
- Department of Endocrine Surgery, King George's Medical University, Lucknow, India
| | - Pooja Ramakant
- Department of Endocrine Surgery, King George's Medical University, Lucknow, India
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22
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Wan CF, Jiang ZY, Wang YQ, Wang L, Fang H, Jin Y, Dong Q, Zhang XQ, Jiang LX. Radiomics of Multimodal Ultrasound for Early Prediction of Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer. Acad Radiol 2025; 32:1861-1873. [PMID: 39690072 DOI: 10.1016/j.acra.2024.11.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 12/19/2024]
Abstract
RATIONALE AND OBJECTIVES To construct and validate a clinical-radiomics model based on radiomics features extracted from two-stage multimodal ultrasound and clinicopathologic information for early predicting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients treated with NAC. MATERIALS AND METHODS Consecutive women with biopsy-proven breast cancer undergoing multimodal US pretreatment and after two cycles of NAC and followed by surgery between January 2014 and November 2023 were retrospectively collected for clinical-radiomics model construction (n = 274) and retrospective test (n = 134). The predictive performance of it was further tested in a subsequent prospective internal test set recruited between January 2024 to July 2024 (n = 76). Finally, a total of 484 patients were enrolled. The clinical-radiomics model predictive performance was compared with radiomics model, clinical model and radiologists' visual assessment by area under the receiver operating characteristic curve (AUC) analysis and DeLong test. RESULTS The proposed clinical-radiomics model obtained the AUC values of 0.92 (95%CI: 0.88, 0.94) and 0.85 (95%CI: 0.79, 0.89) in retrospective and prospective test sets, respectively, which were significantly higher than that those of the radiomics model (AUCs: 0.75-0.85), clinical model (AUCs: 0.68-0.72) and radiologists' visual assessments (AUCs:0.59-0.68) (all p < 0.05). In addition, the predictive efficacy of the radiologists was improved under the assistance of the clinical-radiomics model significantly. CONCLUSION The clinical-radiomics model developed in this study, which integrated clinicopathologic information and two-stage multimodal ultrasound features, was able to early predict pCR to NAC in breast cancer patients with favorable predictive effectiveness.
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Affiliation(s)
- Cai-Feng Wan
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (C-f.W., Y-q.W., L.W., H.F., Y.J., Q.D., L-x.J.)
| | - Zhuo-Yun Jiang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China (Z-y.J.)
| | - Yu-Qun Wang
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (C-f.W., Y-q.W., L.W., H.F., Y.J., Q.D., L-x.J.)
| | - Lin Wang
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (C-f.W., Y-q.W., L.W., H.F., Y.J., Q.D., L-x.J.)
| | - Hua Fang
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (C-f.W., Y-q.W., L.W., H.F., Y.J., Q.D., L-x.J.)
| | - Ye Jin
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (C-f.W., Y-q.W., L.W., H.F., Y.J., Q.D., L-x.J.)
| | - Qi Dong
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (C-f.W., Y-q.W., L.W., H.F., Y.J., Q.D., L-x.J.)
| | - Xue-Qing Zhang
- Department of Pathology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (X-q.Z.)
| | - Li-Xin Jiang
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China (C-f.W., Y-q.W., L.W., H.F., Y.J., Q.D., L-x.J.).
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Antonini M, Mattar A, Pereira da Costa Pinheiro DJ, Maia IB, Teixeira MD, Amorim AG, Ferraro O, Chrispim de Oliveira L, Ramos MDNM, Cavalcante FP, Zerwes F, Madeira M, Barroso-Sousa R, de Camargo Millen E, Frasson AL, Brenelli FP, Facina G, Fenile R, Gebrim LH, Real JM. Disparities in access to anti-HER2 therapies in neoadjuvant chemotherapy: A prognostic analysis based on real-world data comparing Brazil's public and private healthcare systems. Breast 2025; 80:104417. [PMID: 39983435 PMCID: PMC11893340 DOI: 10.1016/j.breast.2025.104417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/08/2025] [Accepted: 02/06/2025] [Indexed: 02/23/2025] Open
Abstract
BACKGROUND Trastuzumab has significantly improved the treatment of HER2-positive breast cancer, particularly in the neoadjuvant setting, where its combination with chemotherapy increases the pathologic complete response (pCR) rate. This retrospective cohort study assesses the implications of disparities in access to trastuzumab within the Brazilian public healthcare system, focusing on pCR, overall survival (OS) and disease-free survival (DFS) in non-metastatic, HER2-positive breast cancer patients undergoing neoadjuvant chemotherapy (NAC). METHODS The study was conducted in the Hospital Pérola Byington (PEROLA), a public institution, and in the Hospital do Servidor Público Estadual (HSPE), a private institution. pCR was defined as the absence of residual invasive or in situ tumors in the breast and axillary nodes. OS and DFS were calculated by Kaplan-Meier survival analysis for a 5-year period. RESULTS From 2011 to 2020, 381 patients at PEROLA and 78 at HSPE underwent NAC. Trastuzumab availability was higher at HSPE (83.4 % vs. 60.0 %, p < 0.0001). Use of trastuzumab correlated with significantly higher pCR rates at both the PEROLA (54.3 % vs. 26.4 %, p < 0.0001) and the HSPE (52.7 % vs. 26.4 %, p < 0.0001). HER2-positive patients with pCR at HSPE also had better OS (80 % vs. 61 %, p < 0.0001) and DFS (89 % vs. 67 %, p < 0.0001) compared to those at PEROLA. CONCLUSION There were significant differences in the provision of trastuzumab between the public and private healthcare systems, adversely affecting clinical outcomes and patient survival. The current data highlight the pressing need to address equity in cancer treatment to improve prognosis for every patient.
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Affiliation(s)
- Marcelo Antonini
- Department of Breast Surgery, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo, SP, Brazil; Centro de Desenvolvimento de Ensino e Pesquisa do Instituo de Assistência Médica ao Servidor Público Estadual (CEDEP - IAMSPE), São Paulo, SP, Brazil; BBREAST - Brazilian Breast Cancer Association Team, São Paulo, SP, Brazil.
| | - André Mattar
- BBREAST - Brazilian Breast Cancer Association Team, São Paulo, SP, Brazil; Department of Breast Surgery, Women's Health Hospital, São Paulo, SP, Brazil; Breast Surgeon at Oncoclínicas, São Paulo, SP, Brazil.
| | | | - Isabela Bastos Maia
- Department of Breast Surgery, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo, SP, Brazil.
| | | | | | - Odair Ferraro
- Department of Breast Surgery, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo, SP, Brazil.
| | | | | | - Francisco Pimentel Cavalcante
- BBREAST - Brazilian Breast Cancer Association Team, São Paulo, SP, Brazil; Department of Breast Surgery, Hospital Geral de Fortaleza Fortaleza, CE, Brazil.
| | - Felipe Zerwes
- BBREAST - Brazilian Breast Cancer Association Team, São Paulo, SP, Brazil; Department of Breast Surgery, Medical School of the Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
| | - Marcelo Madeira
- Department of Breast Surgery, Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, SP, Brazil.
| | | | - Eduardo de Camargo Millen
- BBREAST - Brazilian Breast Cancer Association Team, São Paulo, SP, Brazil; Breast Surgeon at Americas Oncologia, Rio de Janeiro, RJ, Brazil.
| | - Antonio Luiz Frasson
- BBREAST - Brazilian Breast Cancer Association Team, São Paulo, SP, Brazil; Breast Surgeon at Hospital Albert Einstein, São Paulo, SP, Brazil.
| | - Fabricio Palermo Brenelli
- BBREAST - Brazilian Breast Cancer Association Team, São Paulo, SP, Brazil; Department of Breast Surgery, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
| | - Gil Facina
- Department of Ginecology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - Rogério Fenile
- Department of Mastology of Hospital Ipiranda, São Paulo, SP, Brazil.
| | | | - Juliana Monte Real
- Department of Breast Surgery, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo, SP, Brazil; Centro de Desenvolvimento de Ensino e Pesquisa do Instituo de Assistência Médica ao Servidor Público Estadual (CEDEP - IAMSPE), São Paulo, SP, Brazil.
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24
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Shah M, Rath S, Gulia S, Bhargava P, Sekar A, Rane S, Bajpai J, Shet T, Desai S, Sarin R, Pathak R, Popat P, Parab P, Kembhavi Y, Jethwa D, Dutta S, Patil A, Nair N, Rane P, Shetake A, Kolkur M, Joshi S, Badwe RA, Gupta S. Retrospective Study to Determine Factors Influencing Outcome in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Neoadjuvant Chemotherapy. JCO Glob Oncol 2025; 11:e2400365. [PMID: 40267382 DOI: 10.1200/go-24-00365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 02/01/2025] [Accepted: 03/13/2025] [Indexed: 04/25/2025] Open
Abstract
PURPOSE There are scant data on patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with neoadjuvant therapy (NAT) in real-world settings with limited access to HER2-targeted therapy. METHODS This was a retrospective analysis of patients with nonmetastatic, HER2-positive breast cancer treated with NAT between January 2014 and December 2018 to determine factors affecting pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). RESULTS The cohort comprised 1,004 patients with a median age of 47 years, 533 (53.1%) with clinical T3/T4 tumors, 466 (46.4%) with clinical N2/3 status, and 527 (52.5%) with hormone receptor-positive disease. Trastuzumab was given to 528 (52.6%) patients in the neoadjuvant setting and 711 (70.8%) patients in neoadjuvant and/or postoperative settings. pCR was achieved in 226 (22.5%) patients; the 5-year EFS in the whole cohort, pCR group, and no-pCR group was 63.5% (95% CI, 60.36 to 66.63), 86.1% (95% CI, 81.59 to 90.60), and 57% ([95% CI, 53.47 to 60.52]; P < .001), respectively. In multivariable analysis in the full cohort, smaller tumor size (cT1/T2 v cT3/T4), higher grade (III v II), hormone receptor-negative status, and use of neoadjuvant HER2-targeted therapy were significantly associated with higher pCR, and smaller tumor size (cT1/T2 v cT3/T4), lower node involvement (cN0/N1 v cN2/N3), achievement of pCR, and receiving trastuzumab were significantly associated with higher EFS and OS. CONCLUSION In a setting with constrained access to HER2-targeted therapy, lower clinical tumor burden and receiving trastuzumab were significantly associated with increased pCR and survival in patients with HER2-positive breast cancer treated with NAT. Efforts should be made to enhance early diagnosis and access to HER2-targeted therapy worldwide.
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Affiliation(s)
- Minit Shah
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sushmita Rath
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Seema Gulia
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Anbarasan Sekar
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Swapnil Rane
- Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Jyoti Bajpai
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Tanuja Shet
- Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sangeeta Desai
- Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rajiv Sarin
- Department of Radiation Therapy, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rima Pathak
- Department of Radiation Therapy, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Palak Popat
- Department of Radio-Diagnosis, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Pallavi Parab
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Yogesh Kembhavi
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Dinesh Jethwa
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Snigdha Dutta
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Asawari Patil
- Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Nita Nair
- Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Pallavi Rane
- Department of Biostatistics, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Ankush Shetake
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manali Kolkur
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shalaka Joshi
- Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rajendra A Badwe
- Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sudeep Gupta
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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25
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Huang Y, Wang X, Cao Y, Lan X, Hu X, Mou F, Chen H, Gong X, Li L, Tang S, Wang L, Zhang J. Nomogram for Predicting Neoadjuvant Chemotherapy Response in Breast Cancer Using MRI-based Intratumoral Heterogeneity Quantification. Radiology 2025; 315:e241805. [PMID: 40232145 DOI: 10.1148/radiol.241805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
Background Intratumoral heterogeneity (ITH) in breast cancer contributes to treatment failure and relapse. Noninvasive methods to quantify ITH are currently limited. Purpose To quantify ITH in breast cancer using pretreatment MRI, develop a nomogram to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and recurrence-free survival (RFS), and investigate biologic pathways associated with nomogram scores. Materials and Methods This retrospective study included patients with breast cancer who underwent NAC at nine centers between April 1988 and December 2023. Tumor regions on MRI scans were clustered and integrated with global pixel distribution patterns to calculate ITH scores. A nomogram for predicting pCR was developed using multivariable logistic regression. A survival dataset was used to evaluate the association between nomogram score and RFS, and a genomics dataset was used to explore the relationship between nomogram score and biologic pathways. Results The study included 1448 women (median age, 49 years [IQR, 43-54 years]). To predict pCR to NAC, the 505 patients from center A served as the training set, and the patients from center B, centers C-F, and center G served as three external validation sets (n = 331, 107, and 384, respectively). The survival set included patients from centers A and H (n = 179), and the genomics set included patients from center I (n = 74). The ITH score was an independent predictor of pCR (odds ratio, 0.12 [95% CI: 0.03, 0.43]; P < .001). The nomogram model achieved area under the receiver operating characteristic curve values of 0.82, 0.81, and 0.79, respectively, in the three external validation sets. A lower nomogram score was correlated with poorer RFS (hazard ratio, 4.04 [95% CI: 1.90, 8.60]; P < .001) and was associated with upregulation of biologic pathways related to tumor proliferation. Conclusion A nomogram model combining ITH score and clinicopathologic variables showed good performance in predicting pCR to NAC and RFS. Published under a CC BY 4.0 license. Supplemental material is available for this article.
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Affiliation(s)
- Yao Huang
- School of Medicine, Chongqing University, Chongqing, China
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Xiaoxia Wang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Ying Cao
- School of Medicine, Chongqing University, Chongqing, China
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Xiaosong Lan
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Xiaofei Hu
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Fangsheng Mou
- Chongqing Three Gorges University Hospital, Chongqing, China
| | - Huifang Chen
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Xueqin Gong
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Lan Li
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Sun Tang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Lu Wang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
| | - Jiuquan Zhang
- Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer, No. 181 Hanyu Rd, Shapingba District, Chongqing 400030, China
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26
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Ji D, Lan B, Wang J, Ma F, Luo Y, Li Q, Zhang P, Cai R, Li Q, Chen S, Xu B, Fan Y. Clinicopathological Factors That Predict Different Responses of Breast and Axillary Tumors to Neoadjuvant Chemotherapy and Prognosis Among Patients With Node-Positive Breast Cancer: Real World Data. Thorac Cancer 2025; 16:e70035. [PMID: 40176396 PMCID: PMC11965701 DOI: 10.1111/1759-7714.70035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 02/14/2025] [Accepted: 02/25/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND Pathological complete response (pCR) has been proven to be related to prognosis. pCR can be further classified as pCR of the breast (bpCR), pCR of axillary lymph nodes (apCR) or pCR of both tumors. The aim of this study was to elucidate the outcomes and clinicopathological characteristics associated with different patterns of pCR. METHODS Patients with node-positive disease who received neoadjuvant chemotherapy between August 2009 and July 2016 and who achieved pCR in axillary lymph nodes, breast or both were included. Multivariate logistic regression was used to identify factors related to different patterns of pCR. RESULTS Among the 271 patients who were included in the study, 42.1% achieved total pCR, 46.1% achieved ApCR, and 11.8% achieved BpCR. Disease-free survival (DFS) was significantly better in the total pCR group than in the limited pCR groups throughout the entire cohort (p = 0.042). Univariate and multivariate analyses indicated that patients with HR-negative disease and a high Ki-67 proliferation index were more likely to achieve total pCR. Patients with earlier T stage disease were more likely to achieve pCR only in the breast. Among patients who achieved limited pCR, there was no significant difference in terms of whether these patients received intensified adjuvant chemotherapy. CONCLUSIONS Total pCR is still the best marker for predicting survival benefit in patients receiving neoadjuvant chemotherapy, and total pCR is more likely to be achieved in patients with HR-negative disease and a high Ki-67 proliferation index. T stage and N stage may predict apCR and bpCR, respectively.
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Affiliation(s)
- Danyang Ji
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Bo Lan
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jiayu Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yang Luo
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Qing Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Pin Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Ruigang Cai
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Qiao Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Shanshan Chen
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Binghe Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Ying Fan
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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Naldi L, Peri A, Fibbi B. Apelin/APJ: Another Player in the Cancer Biology Network. Int J Mol Sci 2025; 26:2986. [PMID: 40243599 PMCID: PMC11988549 DOI: 10.3390/ijms26072986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 03/17/2025] [Accepted: 03/20/2025] [Indexed: 04/18/2025] Open
Abstract
The apelinergic system exerts multiple biological activities in human pathologies, including cancer. Overactivation of apelin/APJ, which has been detected in many malignant tumors, and the strong correlation with progression-free and overall survival, suggested the role of an oncogene for the apelin gene. Emerging evidence sheds new light on the effects of apelin on cellular functions and homeostasis in cancer cells and supports a direct role for this pathway on different hallmarks of cancer: "sustaining proliferative signaling", "resisting cell death", "activating invasion and metastasis", "inducing/accessing vasculature", "reprogramming cellular metabolism", "avoiding immune destruction" and "tumor-promoting inflammation", and "enabling replicative immortality". This article reviews the currently available literature on the intracellular processes regulated by apelin/APJ, focusing on those pathways correlated with tumor development and progression. Furthermore, the association between the activity of the apelinergic axis and the resistance of cancer cells to oncologic treatments (chemotherapy, immunotherapy, radiation) suggests apelin/APJ as a possible target to potentiate traditional therapies, as well as to develop diagnostic and prognostic applications. This issue will be also covered in the review.
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Affiliation(s)
- Laura Naldi
- “Pituitary Diseases and Sodium Alterations” Unit, AOU Careggi, 50139 Florence, Italy; (L.N.); (B.F.)
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy
| | - Alessandro Peri
- “Pituitary Diseases and Sodium Alterations” Unit, AOU Careggi, 50139 Florence, Italy; (L.N.); (B.F.)
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy
| | - Benedetta Fibbi
- “Pituitary Diseases and Sodium Alterations” Unit, AOU Careggi, 50139 Florence, Italy; (L.N.); (B.F.)
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy
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Zhang N, Shan M, Huang Z, Gao F, Xu B, Kang W, Zhang J, Song L, Liu J, Zhang J, Liu M, Jiang H, Liu X, Shen Z, Zhang P, Nanding A, Zhang G. Screening and exploration of neoadjuvant "de-escalation" therapy for early breast cancer. Front Pharmacol 2025; 16:1574665. [PMID: 40201691 PMCID: PMC11975863 DOI: 10.3389/fphar.2025.1574665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 03/10/2025] [Indexed: 04/10/2025] Open
Abstract
Background Neoadjuvant therapy for breast cancer improves the prognosis of high-risk patients. However, whether pathological completed response (pCR) can be used as a surrogate endpoint for de-escalation therapy in patients who are relatively sensitive to treatment remains to be elucidated. Methods We retrospectively reviewed 143 breast cancer patients, with clinical stage (cStage) II-IIIA who received neoadjuvant chemotherapy and achieved pCR in a short time (within 16 weeks) from 2012 to 2022. The prognosis of patients was analysed using the Kaplan-Meier method, Cox proportional hazards regression models to identify independent clinicopathologic factors affecting prognosis. Results The median follow-up period was 47 months, the overall 4-year disease-free survival (DFS) and overall survival (OS) were 95.3% and 96.9%, respectively, in 143 patients with pCR after neoadjuvant chemotherapy. The 4-year DFS between the postoperative adjuvant chemotherapy and no adjuvant chemotherapy groups was 76.4% and 95.2%, with a significant statistical difference between both groups (P < 0.05). For HER2-positive (HER2+) and Triple negative breast cancer (TNBC), the addition of targeted therapy or platinum-based drugs had no impact on prognosis. Univariate and multivariate analyses of prognosis showed that only postoperative adjuvant chemotherapy significantly affected prognosis. Conclusion Patients with operable cStage II-IIIA breast cancer who achieved pCR after a short period of neoadjuvant chemotherapy have a satisfactory prognosis and may be suitable for chemotherapy "de-escalation." This approach is also a dominant application of neoadjuvant "tailoring therapy."
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Affiliation(s)
- Nana Zhang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Ming Shan
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Zhenfeng Huang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Fei Gao
- Department of Anorectum, Heilongjiang General Hospital of Daqing Oil Field, Daqing, Heilongjiang, China
| | - Bingqi Xu
- Department of Anorectum, Heilongjiang General Hospital of Daqing Oil Field, Daqing, Heilongjiang, China
| | - Wenli Kang
- Department of Oncology, Beidahuang Group General Hospital, Harbin, Heilongjiang, China
| | - Jian Zhang
- Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Li Song
- Department of Oncology, JiaMuSi Tumor Hospital, JiaMuSi, Heilongjiang, China
| | - Jun Liu
- Department of Breast Surgery, Dalian Municipal Friendship Hospital, Dalian, Liaoning, China
| | - Jiawei Zhang
- Department of Oncology, JiaMuSi Tumor Hospital, JiaMuSi, Heilongjiang, China
| | - Mingyang Liu
- Department of Oncology, WangKui County People’s hospital, WangKui, Heilongjiang, China
| | - Haitao Jiang
- Department of Oncology, Hailun People’s Hospital, Suihua, Heilongjiang, China
| | - Xinhang Liu
- Department of Pharmacy, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Zibo Shen
- Biomedical and Life Science Faculty, King’s College London, London, United Kingdom
| | - Peng Zhang
- Faculty of Economics and Management, Baotou Teachers’ College, Baotou, Inner Mongolia Autonomous Region, China
| | - Abiyasi Nanding
- Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Guoqiang Zhang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
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Kim H, Choi JS, Chi SA, Ryu JM, Lee JE, Kim MK, Lee J, Ko ES, Ko EY, Han BK. Digital mammography with AI-based computer-aided diagnosis to predict neoadjuvant chemotherapy response in HER2-positive and triple-negative breast cancer patients: comparison with MRI. Eur Radiol 2025:10.1007/s00330-025-11390-x. [PMID: 40131473 DOI: 10.1007/s00330-025-11390-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 11/28/2024] [Accepted: 01/01/2025] [Indexed: 03/27/2025]
Abstract
OBJECTIVE To investigate whether digital mammography (DM) with artificial intelligence-based computer-aided diagnosis (AI-CAD) predicts pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) breast cancers and compare performance with dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND METHODS In this single-center study, patients who underwent NAC and surgery for HER2-positive or TN cancers between September 2020 and August 2021 were retrospectively selected to develop prediction models for pCR after NAC. From a prospective ASLAN (Avoid axillary Sentinel Lymph node biopsy After Neoadjuvant chemotherapy) trial, HER2-positive and TN cancer patients who underwent NAC and surgery between December 2021 and July 2022 were prospectively selected for model validation. Clinical-pathologic data and DM and MRI scans were obtained before and after NAC. Logistic regression analyses identified factors associated with pCR for model development and four models (clinical-pathologic, MRI, DM-AI-CAD, and combined) were evaluated. RESULTS A total of 259 women (mean age, 53 years ± 10.5 [SD]) constituted the development cohort and 119 (50.8 years ± 11.1) the validation cohort. Age, clinical N stage, estrogen receptor, progesterone receptor, and Ki-67 were incorporated into the clinical-pathologic model. In the validation cohort, the DM-AI-CAD model, applying AI-CAD score ≤ 16 on post-NAC DM as the radiologic CR criterion, showed a higher area under the receiver operating characteristic curve (AUC) compared to the clinical-pathologic model (0.72 vs. 0.62; p = 0.01) for pCR. However, the MRI model showed the highest AUC (0.83), then the combined model (0.78). CONCLUSION The model utilizing post-NAC DM with AI-CAD score ≤ 16 predicted pCR more accurately than the clinical-pathologic model in HER2-positive and TN cancers but was inferior to the MRI model. KEY POINTS Question The performance of digital mammography (DM) with AI-based computer-aided diagnosis (AI-CAD) for predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear. Findings The DM-AI-CAD model incorporating AI-CAD score ≤ 16 on post-NAC DM predicted pCR more accurately than the clinical-pathologic model but not the MRI model. Clinical relevance The DM-AI-CAD model has potential to predict pCR after NAC in breast cancer patients for whom MRI is unavailable or contraindicated.
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Affiliation(s)
- Haejung Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Soo Choi
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, Korea.
| | - Sang Ah Chi
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Jai Min Ryu
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeong Eon Lee
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Myoung Kyoung Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeongmin Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Sook Ko
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Young Ko
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Boo-Kyung Han
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Zheng C, Zheng D, Zhang Y, Lin R, Zheng Z. A population‑based propensity score matching analysis of neoadjuvant compared to adjuvant chemotherapy in luminal breast cancer. Sci Rep 2025; 15:9568. [PMID: 40113956 PMCID: PMC11926370 DOI: 10.1038/s41598-025-93934-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 03/10/2025] [Indexed: 03/22/2025] Open
Abstract
This study evaluated the long-term prognosis of patients with luminal (HR+/HER2-) breast cancer who underwent either neoadjuvant or adjuvant chemotherapy. Between January 2014 and December 2018, 1065 h+/HER2- breast cancer patients were retrospectively analyzed. Each patient receiving neoadjuvant chemotherapy was matched with two patients receiving adjuvant chemotherapy using a 1:2 propensity score matching (PSM) approach. After matching, 47 neoadjuvant chemotherapy patients and 89 adjuvant chemotherapy patients were included. The clinical and pathological characteristics of both groups were compared, and risk factors for postoperative events were assessed alongside a survival analysis. Following propensity score matching, the characteristics of the two groups were well balanced. The study identified lower progesterone receptor (PR) expression, histological grade III, and lymph node metastasis as independent risk factors for recurrence-free survival (RFS). No significant difference in RFS was observed between neoadjuvant and adjuvant chemotherapy. It is recommended that patients with HR+/HER2- breast cancer who exhibit a poor response to neoadjuvant chemotherapy should undergo early surgery, with personalized treatment decisions based on postoperative pathological findings.
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Affiliation(s)
- Chenhui Zheng
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Danni Zheng
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Yuzhu Zhang
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Renzhi Lin
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Zhibao Zheng
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.
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de Souza JS, Reitz LK, Copetti CLK, Moreno YMF, Vieira FGK, Di Pietro PF. Lower Adherence to Lifestyle Recommendations of the World Cancer Research Fund/American Institute for Cancer Research (2018) Is Associated with Decreased Overall 10-Year Survival in Women with Breast Cancer. Nutrients 2025; 17:1001. [PMID: 40290024 PMCID: PMC11945812 DOI: 10.3390/nu17061001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND/OBJECTIVES The 2018 lifestyle recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) have been associated with lower incidence of breast cancer, but their impact on mortality, survival, and recurrence of the disease is not known. This study aimed to investigate the association between adherence to WCRF/AICR recommendations on mortality, overall 10-year survival, and recurrence in women diagnosed with breast cancer. METHODS This prospective study included 101 women diagnosed with breast cancer between 2006 and 2011. Food consumption, body weight, and physical activity data were collected at diagnosis to calculate the WCRF/AICR score. Mortality, survival, and recurrence data were collected in 2020-2021. Kaplan-Meier curves and Cox proportional hazards regression models were applied to verify the association between WCRF/AICR score and its components with outcomes. RESULTS Women with lower adherence to the WCRF/AICR score (1st tertile, which was the reference group for regression models) had lower chance of 10-year overall survival when compared to patients with higher scores (2nd and 3rd tertiles, n = 67) (p = 0.025). Consumption of sugary drinks increased the chance of all-cause mortality (p = 0.005) and daily fiber intake increased the chance of overall 10-year survival (p = 0.027). CONCLUSIONS It is suggested that adherence to WCRF/AICR recommendations before breast cancer treatment may contribute to better life expectancy.
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Affiliation(s)
- Jaqueline Schroeder de Souza
- Post Graduate Program in Nutrition, Federal University of Santa Catarina, Florianopolis 88040-900, Brazil; (J.S.d.S.); (C.L.K.C.); (Y.M.F.M.); (F.G.K.V.)
| | - Luiza Kuhnen Reitz
- Florianopolis Specialized Oncology Center, Florianopolis 88032-005, Brazil;
| | - Cândice Laís Knöner Copetti
- Post Graduate Program in Nutrition, Federal University of Santa Catarina, Florianopolis 88040-900, Brazil; (J.S.d.S.); (C.L.K.C.); (Y.M.F.M.); (F.G.K.V.)
| | - Yara Maria Franco Moreno
- Post Graduate Program in Nutrition, Federal University of Santa Catarina, Florianopolis 88040-900, Brazil; (J.S.d.S.); (C.L.K.C.); (Y.M.F.M.); (F.G.K.V.)
| | - Francilene Gracieli Kunradi Vieira
- Post Graduate Program in Nutrition, Federal University of Santa Catarina, Florianopolis 88040-900, Brazil; (J.S.d.S.); (C.L.K.C.); (Y.M.F.M.); (F.G.K.V.)
| | - Patricia Faria Di Pietro
- Post Graduate Program in Nutrition, Federal University of Santa Catarina, Florianopolis 88040-900, Brazil; (J.S.d.S.); (C.L.K.C.); (Y.M.F.M.); (F.G.K.V.)
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Ni P, Li Y, Wang Y, Wei X, Liu W, Wu M, Zhang L, Zhang F. Construction of a nomogram prediction model for the pathological complete response after neoadjuvant chemotherapy in breast cancer: a study based on ultrasound and clinicopathological features. Front Oncol 2025; 15:1459914. [PMID: 40115015 PMCID: PMC11922718 DOI: 10.3389/fonc.2025.1459914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 02/18/2025] [Indexed: 03/22/2025] Open
Abstract
Objective To explore the application value of ultrasound in evaluating the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer and construct a nomogram prediction model for pathological complete response (pCR) following different cycles of NAC based on ultrasound and clinicopathological features, and further investigate the optimal prediction cycle. Methods A total of 249 breast cancer patients who received NAC were recruited. Ultrasound assessment was performed before NAC and after two cycles of NAC (NAC2), four cycles of NAC (NAC4), and six cycles of NAC (NAC6). All patients underwent surgical resection after NAC6 and the samples were sent for histopathological and immunohistochemical examination. Clinical efficacy was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST). Pathological efficacy was determined according to the Miller-Payne evaluation system (MP); grade 5 was classified as pCR group, while Grades 1-4 were classified as the non-pCR group (npCR). The patients were randomly divided into the training set and the validation set at a ratio of 7:3. The ultrasound and clinicopathological features of the training set were compared, and a nomogram prediction model was constructed based on these features. Finally, the ROC curve, calibration curve, and DCA were used for verification. Result Among the 249 patients, 71 (28.5%) achieved pCR, whereas the remaining 178 (71.5%) exhibited npCR. The maximum tumor diameter measured by ultrasound after NAC6 was 1.20 (0.70, 2.10) cm, which was significantly positively correlated with the maximum tumor diameter measured by pathology after surgical resection (r=0.626, P<0.05). In the training set, multivariate logistic regression analysis revealed that tumor size, posterior echo, RECIST evaluation, and PR status were significantly correlated with pCR after NAC2, NAC4, and NAC6 (P<0.05). These indicators were incorporated into static and dynamic nomogram models, demonstrating high predictive performance, calibration, and clinical value in both the training and validation sets. Conclusion Regardless of the cycle of NAC, patients with a small tumor, no posterior shadow, a valid RECIST, and a negative PR were more likely to achieve pCR. Evaluation after NAC2 can provide early predictive value in clinical practice.
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Affiliation(s)
- Pingjuan Ni
- Department of Ultrasound, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yuan Li
- Department of Ultrasound, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yu Wang
- Department of Ultrasound, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Xiuliang Wei
- Department of Ultrasound, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Wenhui Liu
- Department of Ultrasound, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Mei Wu
- Department of Ultrasound, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Lulu Zhang
- Department of Pathology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Feixue Zhang
- Department of Ultrasound, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
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Akula V, Chen L, Acikgoz Y, Klein K, Yavuz BG, Cevik L, Demir T, Manne A, Sahin I, Kaseb A, Hasanov E. Neoadjuvant immune checkpoint inhibitors for hepatocellular carcinoma. NPJ Precis Oncol 2025; 9:60. [PMID: 40050446 PMCID: PMC11885445 DOI: 10.1038/s41698-025-00846-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 02/24/2025] [Indexed: 03/09/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC treatment is challenging; surgical resection is the primary curative treatment for early-stage disease, but recurrence rates are high. Immune checkpoint inhibitors (ICIs) are a promising neoadjuvant treatment that can reduce recurrence rates and mortality after surgery and achieve complete/partial responses. Clinical trials provide strong evidence for the efficacy and safety of ICI monotherapy for neoadjuvant HCC treatment.
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Affiliation(s)
- Vinita Akula
- Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Lily Chen
- Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Yusuf Acikgoz
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Katherine Klein
- Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Betul Gok Yavuz
- Department of Medicine, University of Missouri, Columbia, MO, USA
| | - Lokman Cevik
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Tarik Demir
- Division of Hematology and Oncology Developmental Therapeutics Institute, Northwestern University, Chicago, IL, USA
| | - Ashish Manne
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Ilyas Sahin
- Division of Hematology & Oncology, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elshad Hasanov
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
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Yoshino T, Zhang Z, Sato R, Lipkowitz S, Fujii T. Revisiting surrogacy of pathological complete response for long-term survival in triple-negative breast cancer. JNCI Cancer Spectr 2025; 9:pkaf022. [PMID: 39992221 PMCID: PMC11932712 DOI: 10.1093/jncics/pkaf022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 01/03/2025] [Accepted: 02/10/2025] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND Pathological complete response has been used as a primary endpoint in neoadjuvant trials in early stage triple-negative breast cancer, and the Food and Drug Administration accepted pathological complete response as a surrogate endpoint for long-term survival outcomes in high-risk early stage breast cancer for new drug approval. However, there is insufficient trial-level data to robustly support pathological complete response as a surrogate for long-term survival in triple-negative breast cancer. METHODS A systematic literature review was performed to identify randomized clinical trials of neoadjuvant systemic therapy for patients with clinical stage I-III triple-negative breast cancer. Data of odds ratios (ORs) for pathological complete response and hazard ratios (HRs) for event-free survival and overall survival were extracted. Disease-free survival was used as an alternative when event-free survival data were unavailable. A linear regression model on a logarithmic scale, coefficient of difference, and 95% confidential interval (CI) were calculated to assess the trial-level association between odds ratio for pathological complete response and hazard ratio for overall survival and event-free survival. RESULTS Eight trials with 2342 patients were included. Three trials tested immune checkpoint inhibitors. Coefficient of difference (R2) was 0.2 for hazard ratio of event-free survival (95% CI = 0.17 to 0.22, P = .27), and R2 for hazard ratio of overall survival was 0.19 (95% CI = 0.17 to 0.22, P = .33). CONCLUSIONS There is no strong evidence to support using pathological complete response as a surrogate marker for event-free survival or overall survival in early stage triple-negative breast cancer at the trial level. Because of the necessity of minimizing drug approval delay with reliable long-term outcome, further studies of surrogate markers in early stage triple-negative breast cancer are warranted.
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Affiliation(s)
- Toru Yoshino
- Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States
- Department of Internal Medicine, Nakagami Hospital, Okinawa 904-2142, Japan
- Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, United States
| | - Zao Zhang
- Department of Internal Medicine, The Queen’s Medical Center, Honolulu, HI 96813, United States
| | - Ryota Sato
- Department of Internal Medicine, The Queen’s Medical Center, Honolulu, HI 96813, United States
| | - Stanley Lipkowitz
- Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States
| | - Takeo Fujii
- Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States
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Yuan Y, Liu X, Xu G, Zhang J, Chen L, Long X. Comparative efficacy and safety of pyrotinib plus trastuzumab versus trastuzumab plus pertuzumab and trastuzumab monotherapy in neoadjuvant treatment of HER2-positive breast cancer: A systematic review and meta-analysis. Cancer Treat Rev 2025; 134:102901. [PMID: 39986012 DOI: 10.1016/j.ctrv.2025.102901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 02/09/2025] [Accepted: 02/10/2025] [Indexed: 02/24/2025]
Abstract
INTRODUCTION HER2-positive breast cancer is an aggressive subtype that benefits from targeted therapies. Some studies have shown that pyrotinib (P) plus trastuzumab (H) has a good efficacy against early or locally advanced HER2-positive breast cancer. However, there is still no systematic review and meta-analysis supporting the efficacy and safety of pyrotinib plus trastuzumab versus standard regimens in the neoadjuvant treatment of early or locally advanced breast cancer. This study is the first systematic review and meta-analysis to compare the efficacy and safety of pyrotinib combined with trastuzumab versus trastuzumab combined with pertuzumab (Per) and trastuzumab monotherapy in the neoadjuvant treatment of HER2-positive breast cancer. METHODS We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, CNKI, Wan Fang and VIP databases for relevant studies published up to August 30th, 2024. RCTs, cohort studies and retrospective studies with HER2-positive breast cancer patients who had not received breast cancer-related treatments previously were included. Treatment of P + H, H or Per + H arms with chemotherapy combined with pyrotinib plus trastuzumab, trastuzumab or pertuzumab plus trastuzumab as neoadjuvant treatment. The primary outcome was the total pathological complete response (tpCR), and secondary outcomes included breast pathological complete response (bpCR), ORR, DCR, and grade III/IV AEs. The quality of evidence was assessed using the GRADE. RESULTS A total of nine studies (4 RCTs, 1 prospective cohort study and 4 retrospective analysis) involving 1745 patients were included. The P + H arm showed no significant difference in tpCR compared to Per + H (RR: 0.94, 95 % CI: 0.80-1.11, p = 0.46) but demonstrated a significant improvement in tpCR over trastuzumab monotherapy (RR: 1.83, 95 % CI: 1.56-2.15, p < 0.001). This finding was further confirmed in meta-analysis of RCTs (RR: 1.87, 95 % CI: 1.42-2.47, p < 0.001). The P + H arm had a higher incidence of grade III/IV diarrhea (RR: 10.54, 95 % CI: 5.96-18.63, p < 0.001) but similar rates of other AEs compared to the H arm. The evidence quality for tpCR (P + H vs. H, RCT) was high, and that for tpCR (P + H vs. H) was moderate, while that for tpCR (P + H vs. Per + H) was low. CONCLUSIONS Pyrotinib combined with trastuzumab may offer an effective neoadjuvant treatment option for HER2-positive breast cancer, with a superior efficacy over trastuzumab alone. However, pyrotinib plus trastuzumab did not show better efficacy compared with Per + H. Pyrotinib plus trastuzumab was associated with more diarrhrea than trastuzumab monotherapy. In addition, P + H is less cost-effective compared with the combination of Per + H.
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Affiliation(s)
- Ye Yuan
- Sichuan Integrative Medicine Hospital, China.
| | - Xumei Liu
- Chengdu Anticancer Bioscience, China
| | - Gaifeng Xu
- Sichuan Integrative Medicine Hospital, China
| | - Ji Zhang
- Sichuan Integrative Medicine Hospital, China
| | - Li Chen
- Sichuan Integrative Medicine Hospital, China
| | - Xin Long
- Sichuan Integrative Medicine Hospital, China.
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Huang Y, Shi Z, Zhu T, Zhou T, Li Y, Li W, Qiu H, Wang S, He L, Wu Z, Lin Y, Wang Q, Gu W, Gu C, Song X, Zhou Y, Guan D, Wang K. Longitudinal MRI-Driven Multi-Modality Approach for Predicting Pathological Complete Response and B Cell Infiltration in Breast Cancer. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413702. [PMID: 39921294 PMCID: PMC11948082 DOI: 10.1002/advs.202413702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/30/2024] [Indexed: 02/10/2025]
Abstract
Accurately predicting pathological complete response (pCR) to neoadjuvant treatment (NAT) in breast cancer remains challenging due to tumor heterogeneity. This study enrolled 2279 patients across 12 centers and develops a novel multi-modality model integrating longitudinal magnetic resonance imaging (MRI) spatial habitat radiomics, transcriptomics, and single-cell RNA sequencing for predicting pCR. By analyzing tumor subregions on multi-timepoint MRI, the model captures dynamic intra-tumoral heterogeneity during NAT. It shows superior performance over traditional radiomics, with areas under the curve of 0.863, 0.813, and 0.888 in the external validation, immunotherapy, and multi-omics cohorts, respectively. Subgroup analysis shows its robustness across varying molecular subtypes and clinical stages. Transcriptomic and single-cell RNA sequencing analysis reveals that high model scores correlate with increased immune activity, notably elevated B cell infiltration, indicating the biological basis of the imaging model. The integration of imaging and molecular data demonstrates promise in spatial habitat radiomics to monitor dynamic changes in tumor heterogeneity during NAT. In clinical practice, this study provides a noninvasive tool to accurately predict pCR, with the potential to guide treatment planning and improve breast-conserving surgery rates. Despite promising results, the model requires prospective validation to confirm its utility across diverse patient populations and clinical settings.
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Affiliation(s)
- Yu‐Hong Huang
- Department of Breast CancerCancer CenterGuangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityNo. 106 Zhongshan Second Road, Yuexiu DistrictGuangzhouGuangdong Province510080China
| | - Zhen‐Yi Shi
- Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong Province510515China
- Guangdong Key Laboratory of Single Cell Technology and ApplicationSouthern Medical University, GuangzhouGuangdong Province510515China
| | - Teng Zhu
- Department of Breast CancerCancer CenterGuangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityNo. 106 Zhongshan Second Road, Yuexiu DistrictGuangzhouGuangdong Province510080China
| | - Tian‐Han Zhou
- The Department of General SurgeryHangzhou TCM HospitalAffiliated to Zhejiang Chinese Medical UniversityXihu DistrictHangzhouZhejiang Province310000China
| | - Yi Li
- Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong Province510515China
- Guangdong Key Laboratory of Single Cell Technology and ApplicationSouthern Medical University, GuangzhouGuangdong Province510515China
| | - Wei Li
- Department of Breast CancerCancer CenterGuangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityNo. 106 Zhongshan Second Road, Yuexiu DistrictGuangzhouGuangdong Province510080China
| | - Han Qiu
- Galactophore DepartmentJingzhou Hospital Affiliated to Yangtze UniversityShashi DistrictJingzhou434000China
| | - Si‐Qi Wang
- Department of BiostatisticsHarvard T.H. Chan School of Public HealthBostonMA02115USA
| | - Li‐Fang He
- Breast CenterCancer Hospital of Shantou University Medical CollegeJinping DistrictShantouGuangdong Province515000China
| | - Zhi‐Yong Wu
- Clinical research center & Breast disease diagnosis and treatment centerShantou Central HospitalNo. 114 Waima Road, Jinping DistrictShantouGuangdong Province515000China
| | - Ying Lin
- Breast Disease Center, The First Affiliated HospitalSun Yat‐sen UniversityNo. 58 Zhongshan Second Road, Yuexiu DistrictGuangzhouGuangdong Province510080China
| | - Qian Wang
- Department of RadiologyThe Affiliated Huaian No.1 People's Hospital of Nanjing Medical UniversityHuaiyin DistrictHuaianJiangsu Province223001China
| | - Wen‐Chao Gu
- Department of Artificial Intelligence MedicineGraduate School of MedicineChiba UniversityChiba263‐8522Japan
| | - Chang‐Cong Gu
- Department of Medical ImagingThe First Hospital of QinhuangdaoHaigang DistrictQinhuangdaoHebei Province066000China
| | - Xin‐Yang Song
- Department of RadiologyThe First Affiliated Hospital of Jinan UniversityNo. 613 Huangpu West Road, Tianhe DistrictGuangzhouGuangdong510627China
| | - Yang Zhou
- Department of PathologyThe Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical UniversityNo. 29 Xinglong LaneChangzhouJiangsu Province213164China
| | - Dao‐Gang Guan
- Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong Province510515China
- Guangdong Key Laboratory of Single Cell Technology and ApplicationSouthern Medical University, GuangzhouGuangdong Province510515China
| | - Kun Wang
- Department of Breast CancerCancer CenterGuangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityNo. 106 Zhongshan Second Road, Yuexiu DistrictGuangzhouGuangdong Province510080China
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Szwiec M, Tomiczek-Szwiec J, Marciniak W, Derkacz R, Huzarski T, Cybulski C, Gronwald J, Osowiecka K, Sibilski R, Narod SA, Lubiński J. The Effect of Blood Selenium Level on the pCR Rate in Breast Cancer Patient Receiving Neoadjuvant Chemotherapy. Cancers (Basel) 2025; 17:839. [PMID: 40075686 PMCID: PMC11898521 DOI: 10.3390/cancers17050839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
PURPOSE Among patients treated with neoadjuvant chemotherapy (NAC), a high survival rate is observed for those who experience a pathological complete response (pCR). Various tumor factors are predictive of a pCR, but few host factors have been studied.We sought to inquire whether or not a patient's blood selenium level prior to treatment was predictive of a pCR. METHODS We studied 329 women diagnosed with primary invasive breast cancer who were treated with neoadjuvant chemotherapy (NAC). We included patients with HER2-positive (n = 183) or triple-negative breast cancer (n = 146). Blood was collected before the initiation of treatment. Blood levels of selenium were quantified by mass spectroscopy. Each patient was assigned to one of three tertiles based on the distribution of blood selenium levels in the entire cohort. Patients with triple-negative breast cancer (TNBC) were treated with a range of combination chemotherapies. Patients with HER2-positive breast cancer received anti-HER2 treatment based on trastuzumab alone or trastuzumab and pertuzamab. After treatment, each patient was classified as having pCR or no pCR. RESULTS In the entire cohort, the pCR rate was 59.0% for women in the highest tertileof blood selenium (≥107.19 μg/L) compared to 39.0% for women in the lowest tertile (≤94.29 μg/L) (p = 0.003). CONCLUSIONS A high selenium level is predictive of pCR in women treated for HER2-positive or triple-negative breast cancer. If confirmed, this observation may lead to a study investigating if selenium supplementation improves pCR rates and survival in breast cancer women receiving NAC.
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Affiliation(s)
- Marek Szwiec
- Department of Surgery and Oncology, University of ZielonaGóra, Zyty 28, 65-046 Zielona Góra, Poland; (M.S.); (R.S.)
| | - Joanna Tomiczek-Szwiec
- Department of Biology and Genetics, Faculty of Medicine, University of Opole, Oleska 48, 45-052 Opole, Poland;
- Clinical Department of Oncological Gynecologyat the Oncology Centre in Opole, 45-061 Opole, Poland
| | - Wojciech Marciniak
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Róża Derkacz
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Tomasz Huzarski
- Department of Clinical Genetics and Pathology, University of ZielonaGóra, ul. Zyty 28, 65-046 Zielona Góra, Poland;
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, ul. UniiLubelskiej 1, 71-252 Szczecin, Poland; (C.C.); (J.G.)
| | - Cezary Cybulski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, ul. UniiLubelskiej 1, 71-252 Szczecin, Poland; (C.C.); (J.G.)
| | - Jacek Gronwald
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, ul. UniiLubelskiej 1, 71-252 Szczecin, Poland; (C.C.); (J.G.)
| | - Karolina Osowiecka
- Department of Psychology and Sociology of Health and Public Health, School of Public Health, University of Warmia and Mazury in Olsztyn, Al. Warszawska 30, 11-041 Olsztyn, Poland;
| | - Robert Sibilski
- Department of Surgery and Oncology, University of ZielonaGóra, Zyty 28, 65-046 Zielona Góra, Poland; (M.S.); (R.S.)
| | - Steven A. Narod
- Women’s College Research Institute, Toronto, ON M5S 1B2, Canada;
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
| | - Jan Lubiński
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, ul. UniiLubelskiej 1, 71-252 Szczecin, Poland; (C.C.); (J.G.)
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Foidart P, Jerusalem G. Is adjuvant olaparib standard of care in all high-risk HER2-negative early breast cancer presenting gBRCA1/2 mutations? Gland Surg 2025; 14:257-262. [PMID: 40115853 PMCID: PMC11921398 DOI: 10.21037/gs-24-467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 02/03/2025] [Indexed: 03/23/2025]
Affiliation(s)
- Pierre Foidart
- Department of Medical Oncology, CHU Sart-Tilman and Liege University, Liege, Belgium
| | - Guy Jerusalem
- Department of Medical Oncology, CHU Sart-Tilman and Liege University, Liege, Belgium
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Li W, Onishi N, Gibbs JE, Wilmes LJ, Le NN, Metanat P, Price ER, Joe BN, Kornak J, Yau C, Wolf DM, Magbanua MJM, LeStage B, van ’t Veer LJ, DeMichele AM, Esserman LJ, Hylton NM. MRI-Based Model for Personalizing Neoadjuvant Treatment in Breast Cancer. Tomography 2025; 11:26. [PMID: 40137566 PMCID: PMC11946387 DOI: 10.3390/tomography11030026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 02/19/2025] [Accepted: 02/25/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Functional tumor volume (FTV), measured from dynamic contrast-enhanced MRI, is an imaging biomarker that can predict treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The FTV-based predictive model, combined with core biopsy, informed treatment decisions of recommending patients with excellent responses to proceed to surgery early in a large NAC clinical trial. METHODS In this retrospective study, we constructed models using FTV measurements. We analyzed performance tradeoffs when a probability threshold was used to identify excellent responders through the prediction of pathology complete response (pCR). Individual models were developed within cohorts defined by the hormone receptor and human epidermal growth factor receptor 2 (HR/HER2) subtype. RESULTS A total of 814 patients enrolled in the I-SPY 2 trial between 2010 and 2016 were included with a mean age of 49 years (range: 24 to 77). Among these patients, 289 (36%) achieved pCR. The area under the ROC curve (AUC) ranged from 0.68 to 0.74 for individual HR/HER2 subtypes. When probability thresholds were chosen based on minimum positive predictive value (PPV) levels of 50%, 70%, and 90%, the PPV-sensitivity tradeoff varied among subtypes. The highest sensitivities (100%, 87%, 45%) were found in the HR-/HER2+ sub-cohort for probability thresholds of 0, 0.62, and 0.72; followed by the triple-negative sub-cohort (98%, 52%, 4%) at thresholds of 0.13, 0.58, and 0.67; and HR+/HER2+ (78%, 16%, 8%) at thresholds of 0.34, 0.57, and 0.60. The lowest sensitivities (20%, 0%, 0%) occurred in the HR+/HER2- sub-cohort. CONCLUSIONS Predictive models developed using imaging biomarkers, alongside clinically validated probability thresholds, can be incorporated into decision-making for precision oncology.
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Affiliation(s)
- Wen Li
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - Natsuko Onishi
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - Jessica E. Gibbs
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - Lisa J. Wilmes
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - Nu N. Le
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - Pouya Metanat
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - Elissa R. Price
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - Bonnie N. Joe
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
| | - John Kornak
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158, USA;
| | - Christina Yau
- Department of Surgery, University of California, San Francisco, CA 94158, USA; (C.Y.); (L.J.E.)
| | - Denise M. Wolf
- Department of Laboratory Medicine, University of California, San Francisco, CA 94158, USA; (D.M.W.); (M.J.M.M.); (L.J.v.’t.V.)
| | - Mark Jesus M. Magbanua
- Department of Laboratory Medicine, University of California, San Francisco, CA 94158, USA; (D.M.W.); (M.J.M.M.); (L.J.v.’t.V.)
| | | | - Laura J. van ’t Veer
- Department of Laboratory Medicine, University of California, San Francisco, CA 94158, USA; (D.M.W.); (M.J.M.M.); (L.J.v.’t.V.)
| | - Angela M. DeMichele
- Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;
| | - Laura J. Esserman
- Department of Surgery, University of California, San Francisco, CA 94158, USA; (C.Y.); (L.J.E.)
| | - Nola M. Hylton
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA; (N.O.); (J.E.G.); (L.J.W.); (N.N.L.); (P.M.); (E.R.P.); (B.N.J.); (N.M.H.)
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Liang G, Zhang Q, Luo Y, Zhao Y, Luo B. Efficacy of anlotinib and chemotherapy combination as neoadjuvant therapy in the treatment of pulmonary artery intimal sarcoma: a case report. Front Oncol 2025; 15:1507281. [PMID: 40078190 PMCID: PMC11897571 DOI: 10.3389/fonc.2025.1507281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 02/07/2025] [Indexed: 03/14/2025] Open
Abstract
Pulmonary arterial intimal sarcoma (PAIS) is a rare malignant mesenchymal tumor often associated with an unfavorable prognosis and lacks a standardized treatment approach to date. This report presents a notable case of PAIS treated with neoadjuvant therapy involving anlotinib concomitantly administered with chemotherapy of ifosfamide and pirarubicin, which resulted in a favorable outcome. A 38-year-old man was admitted to our hospital with chest tightness, cough, and dyspnea, all of which had persisted for more than a week. Initial evaluation via chest computed tomography (CT) revealed a sizable posterior mediastinal tumor measuring 11.9 × 7.6 cm. A CT-guided biopsy was performed, and pathological findings confirmed the diagnosis of PAIS. Efficacy evaluation showed slow progress after one cycle of chemotherapy with ifosfamide and pirarubicin. To enhance treatment outcomes, we incorporated anlotinib as a neoadjuvant therapy alongside ifosfamide and pirarubicin. Subsequent CT imaging demonstrated a significant reduction in tumor size, and the patient experienced notable alleviation of symptoms. The patient then underwent surgery, radiation, and subsequently, maintenance treatment with anlotinib for one year. No severe drug-related side effects were observed. The patient achieved progression-free survival of 25 months following administration of anlotinib. Thus, the combination of anlotinib with ifosfamide and pirarubicin demonstrated significant efficacy and safety. This approach holds promise as an effective therapeutic strategy for managing unresectable, locally advanced, or advanced PAIS. However, further clinical studies are necessary to validate these findings.
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Affiliation(s)
| | | | | | - Yuanhua Zhao
- Department of Radiation Oncology, Hubei Cancer Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Luo
- Department of Radiation Oncology, Hubei Cancer Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, China
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Richter FGB, Mattar A, Antonini M, Teixeira MD, Amorim AG, Millen EC, Brenelli FP, Cavalcante FP, Zerwes F, Frasson AL, Lopes RGC, Gebrim LH, Real JM. The relationship between body mass index and pathological complete response in Brazilian breast cancer patients. Sci Rep 2025; 15:6174. [PMID: 39979484 PMCID: PMC11842549 DOI: 10.1038/s41598-025-89841-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 02/07/2025] [Indexed: 02/22/2025] Open
Abstract
Body mass index (BMI) is a key factor in the progression of breast cancer (BC), with conflicting evidence on its influence on pathological complete response (pCR) following neoadjuvant chemotherapy (NAC). Despite these global findings, studies focusing on real-world Brazilian data remain scarce. This study aimed to evaluate the impact of BMI on pCR rates, recurrence-free survival (RFS), and overall survival (OS) in Brazilian women with BC treated with NAC. A retrospective cohort of 1,751 patients with stage I-III invasive primary BC treated between January 2011 and December 2020 at two public healthcare centers Hospital Pérola Byington (HPB) and Hospital do Servidor Público Estadual (HSPE) in Brazil was analyzed. Data included BMI categories (normal, overweight, and obese) and their associations with pCR, RFS, and OS outcomes. Obesity was prevalent (35.5%) among the cohort, with most patients being postmenopausal (50.9%). Tumors were predominantly stage III invasive ductal carcinoma, with triple-negative and luminal B subtypes being the most common. Radical surgery was performed in 79.8% of cases, achieving a pCR rate of 22.3%, and 30.9% of patients experienced recurrence, predominantly systemic (27.7%). No significant differences in pCR, RFS, or OS were observed across BMI categories. BMI was not associated with pCR, RFS, or OS in this large Brazilian cohort, highlighting the need for further studies to explore BMI dynamics during treatment and its potential influence on therapeutic outcomes. Future investigations in diverse healthcare settings may provide additional insights into optimizing breast cancer management across BMI strata.
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Affiliation(s)
| | - André Mattar
- Hospital da Mulher, Av Rio Branco 1080, São Paulo, 01206-001, Brazil.
- Oncoclíncias, São Paulo, Brazil.
| | | | | | | | | | | | | | - Felipe Zerwes
- Pontifícia Universidade Católica-RS, Porto Alegre, Brazil
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Wang J, Wang X, He Y, Wang T, Li J, Fan Z, Ouyang T. Comparison of 10-Year Survival Between Patients With Axillary Pathologic Complete Response After Neoadjuvant Chemotherapy and Patients With Initially Negative Nodes in Breast Cancer. Clin Breast Cancer 2025:S1526-8209(25)00035-7. [PMID: 40038007 DOI: 10.1016/j.clbc.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 02/06/2025] [Indexed: 03/06/2025]
Abstract
PURPOSE We aimed to determine whether patients with cytologically proven node-positive disease who achieved axillary pathologic complete response (ypN0) after neoadjuvant chemotherapy (NAC) have similar survival outcomes to those with initially pathologically negative lymph nodes (pN0). METHODS Patients with cytologically proven node-positive breast cancer who achieved ypN0 after NAC and those with pN0 between June 2005 and March 2012 in a large cancer hospital were reviewed. The relapse-free survival (RFS), distant-disease-free survival (DDFS) and overall survival (OS) of the 2 groups were calculated and compared. RESULTS A total of 2285 patients, including 183 patients with ypN0 and 2102 patients with pN0, were included in this study. The median follow-up time for patients was 121 (range 2-182) months. The 10-year cumulative RFS was 79.7% for ypN0 patients and 90.2% for pN0 patients (log-rank P < .001). The 10-year cumulative DDFS was 81.4% for ypN0 patients and 92.2% for pN0 patients (log-rank P < .001). The 10-year cumulative OS was 86.3% for ypN0 patients and 94.0% for pN0 patients (log-rank P < .001). The multivariable Cox proportional hazards models showed that compared with pN0 patients, ypN0 patients had a 2.00-fold increase in the risk of recurrence (HR = 2.00, 95% CI, 1.33-3.01, P = .001), a 2.34-fold increase in the risk of distant recurrence (HR = 2.34, 95% CI, 1.52-3.62, P < .001) and a 2.10-fold increase in the risk of death (HR = 2.10, 95% CI, 1.25-3.53, P = .005). CONCLUSION Patients with axillary pCR showed inferior RFS, DDFS and OS to patients with pN0.
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Affiliation(s)
- Jiwei Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xing Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yingjian He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Tianfeng Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jinfeng Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhaoqing Fan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing 100142, China.
| | - Tao Ouyang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Peking University Cancer Hospital & Institute, Beijing 100142, China.
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Shen G, Liu Z, Wang M, Zhao Y, Liu X, Hou Y, Ma W, Han J, Zhou X, Ren D, Zhao F, Li Z, Huang S, Chen Y, He Y, Liu Y, Zhu Z, Li Y, Li J, Da M, Mo H, Du F, Cui L, Bai J, Liu Z, Ma F, Zhao J. Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial. Signal Transduct Target Ther 2025; 10:41. [PMID: 39915443 PMCID: PMC11802755 DOI: 10.1038/s41392-025-02137-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 01/03/2025] [Accepted: 01/10/2025] [Indexed: 02/09/2025] Open
Abstract
We aimed to evaluate the efficacy and safety of adding apatinib, to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer (TNBC). In the phase 2 NeoSAC trial, patients with early TNBC received six cycles of apatinib, sintilimab, nab-paclitaxel, and carboplatin followed by surgery. The primary endpoint was pathological complete response (pCR) rate. Specimens collected pre-neoadjuvant therapy and post-surgery were retained for comprehensive analysis of predictive biomarkers and the impact on the tumor microenvironment. Among 34 enrolled patients, 24 achieved pCR (70.6%; 95% confidence interval (CI), 53.0-85.3), and 79.4% (95% CI, 65.1-93.7) had residual cancer burden 0-I. Imaging evaluation showed 21 complete responses (61.8%) and 13 partial responses (38.2%). The most common grade 3-4 adverse events were leukopenia (47%), neutropenia (36%), and thrombocytopenia (24%). The 36-month disease-free survival rate stood at 94.1% with a median follow-up of 39.1 months. Notably, baseline high ImmuneScore, immune cell infiltration, and enrichment of interferon-related pathways correlated with pCR. Comparison of pre-neoadjuvant and post-surgery data revealed that the pCR group treated with this novel regimen exhibited an upregulation of distinct immune cell subsets, thereby activating the tumor microenvironment. Moreover, higher oxeiptosis scores were associated with an increased likelihood of achieving pCR. Following neoadjuvant therapy, the pCR group showed a decrease in oxeiptosis score, whereas the non-pCR group exhibited an increase. Our study suggests that apatinib, sintilimab combined with carboplatin and nab-paclitaxel chemotherapy showed a promising clinical activity and manageable safety profile in early TNBC and merits further study. ClinicalTrials.gov registration: NCT04722718.
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Affiliation(s)
- Guoshuang Shen
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Zhilin Liu
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Miaozhou Wang
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Yi Zhao
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Xinlan Liu
- Medical Oncology Department of General Hospital of Ningxia Medical University, Yinchuan, China
| | - Yujin Hou
- Medical Oncology Department of General Hospital of Ningxia Medical University, Yinchuan, China
| | - Wenbiao Ma
- Department of Oncology, 2nd Ward, Qinghai Provincial People's Hospital (Breast and Thyroid Surgery), Xining, China
| | - Jingqi Han
- Department of pathology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Xiaofeng Zhou
- Department of pathology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Dengfeng Ren
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Fuxing Zhao
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Zitao Li
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Shifen Huang
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Yongzhi Chen
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Yingjian He
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yan Liu
- Department of Public Health, Medical College of Qinghai University, Xining, China
| | - Zijun Zhu
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Yongxin Li
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Jinming Li
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Mengting Da
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
| | - Hongnan Mo
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing),The VIPII Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing, China
| | - Liang Cui
- Geneplus-Beijing Institute, Beijing, China
| | - Jing Bai
- Geneplus-Beijing Institute, Beijing, China
| | - Zhen Liu
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China.
| | - Fei Ma
- State Key Laboratory of Molecular Oncology, Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Jiuda Zhao
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China.
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Connors C, Valente SA, ElSherif A, Escobar P, Chichura A, Kopicky L, Roesch E, Ritner J, McIntire P, Wu Y, Tu C, Lang JE. Real-World Outcomes with the KEYNOTE-522 Regimen in Early-Stage Triple-Negative Breast Cancer. Ann Surg Oncol 2025; 32:912-921. [PMID: 39436619 PMCID: PMC11843215 DOI: 10.1245/s10434-024-16390-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 10/07/2024] [Indexed: 10/23/2024]
Abstract
BACKGROUND This study aimed to determine if the neoadjuvant (NAT) KEYNOTE-522 regimen was associated with higher rates of pathologic complete response (pCR), corresponding to higher rates of breast conservation therapy (BCT) in early-stage triple-negative breast cancer (TNBC) patients. PATIENTS AND METHODS Stage II-III TNBC patients diagnosed between 2019 and 2022 who underwent NAT were analyzed retrospectively. NAT with KEYNOTE-522 versus control NAT were compared for rates of BCT, axillary node dissection (ALND), pCR, and survival outcomes. The prevalence of immune-related adverse events (irAE) from chemoimmunotherapy was recorded. RESULTS Of 240 patients identified: 86 received KEYNOTE-522 and 154 received control. The frequency of pCR was significantly higher in KEYNOTE versus the control cohort, 59.3% and 33.1%, respectively (p = 0.001). There was no significant difference in the rate of BCT between the control (33.1%) and the KEYNOTE-522 (32.1%) groups (p = 0.47). Rates of ALND were significantly lower with KEYNOTE-522 (25.6%) as compared with control (39.6%); p = 0.03. The rate of development of grade 2 or higher irAEs was 34.9%. At a median follow-up of 2.4 years, there was no difference in survival outcomes. BRCA1 patients had high rates of pCR regardless of treatment group, KEYNOTE-522: 80.0% (4/5) and control: 75% (9/12), (p = 1). CONCLUSION This real-world evidence supports the use of the KEYNOTE-522 regimen in patients with early-stage TNBC given the higher pCR rate and corresponding decrease in the rate of ALND. The majority of patients in both NAT cohorts became BCT eligible, but the rate of BCT did not differ between the two groups.
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Affiliation(s)
- Casey Connors
- Department of Breast Surgery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Stephanie A Valente
- Department of Breast Surgery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ayat ElSherif
- Department of Breast Surgery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
- Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Paula Escobar
- Department of Breast Surgery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Anna Chichura
- Department of Breast Surgery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Lauren Kopicky
- Department of Breast Surgery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Erin Roesch
- Department of Medical Oncology, Cleveland Clinic, Cleveland, OH, USA
| | - Julie Ritner
- Department of Radiology, Cleveland Clinic, Cleveland, OH, USA
| | | | - Yueqi Wu
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Chao Tu
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Julie E Lang
- Department of Breast Surgery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
- Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
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45
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Ben Dhia S, Schiappa R, Gal J, Ferrero JM, Bahadoran P, Chapellier C, Bondiau PY. Cyberneo trial investigating the efficacy of stereotactic radiotherapy combined to neoadjuvant chemotherapy for locally advanced breast cancer: 14-years follow-up results. Cancer Radiother 2025; 29:104592. [PMID: 40020436 DOI: 10.1016/j.canrad.2025.104592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/01/2024] [Accepted: 10/02/2024] [Indexed: 03/03/2025]
Abstract
PURPOSE The purpose of the phase I trial named "Cyberneo" was to define the efficacy of the stereotactic radiotherapy using CyberKnife® for locally advanced (stage III) breast tumours combined to a neoadjuvant chemotherapy for patients for whom a conservative surgery could not be considered at the onset. Neoadjuvant chemotherapy consisted of six cycles: three cycles of docetaxel and three cycles of the combination of 5-fluorouracil, epirubicin and cyclophosphamide. Stereotactic radiotherapy using CyberKnife® was performed during the second cycle of chemotherapy. Breast surgery was performed 6 to 8 weeks later and conventional breast irradiation without boost, afterwards. The main objective was to define the maximum tolerated dose of hypofractionated radiotherapy concurrent with neoadjuvant chemotherapy. We present an updated survival data for patients included in this trial and we evaluate the late toxicity of this combination. PATIENTS AND METHODS We updated the survival data of 25 patients treated for a stage III breast cancer between 2007 and 2009 at the Antoine-Lacassagne centre in Nice and included in the Cyberneo trial by recording late toxicity events and aesthetic results. RESULTS With a median follow-up of 12 years (95 % confidence interval [CI]: 10-14 years), 19 patients were in remission (76 %), one patient had a controlled axillary lymph node relapse (4 %) and five patients (20 %) died due to metastatic progression within a median of 5 years after treatment (range: 1-9 years). Nine patients had a complete histological response (36 %). The highest percentage of complete histological response was in the group of patients treated in the fourth stage (28.5Gy in four fractions). Overall survival rate at 14 years was 71 % (95 % CI: [53-94 %]). Two patients developed chronic radiation toxicity during follow-up with a fibrosis (8 %) of which one was in the fourth stage and one in the fifth stage (31.5Gy). Three patients (12 %) had a change of prosthesis after treatment, which for one patient was 24 months after the end of support. CONCLUSION The updated results of the Cyberneo trial with 14 years of follow-up confirm the satisfactory results in terms of local control with an excellent long-term safety profile.
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Affiliation(s)
- Syrine Ben Dhia
- Département de radiothérapie, centre Antoine-Lacassagne, Nice, France.
| | - Renaud Schiappa
- Département d'épidémiologie et de biostatistiques, centre Antoine-Lacassagne, Nice, France
| | - Jocelyn Gal
- Département d'épidémiologie et de biostatistiques, centre Antoine-Lacassagne, Nice, France
| | - Jean-Marc Ferrero
- Département d'oncologie médicale, centre Antoine-Lacassagne, Nice, France
| | | | - Claire Chapellier
- Département d'imagerie médicale, centre Antoine-Lacassagne, Nice, France
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Chen R, Iwai T, Tajima H, Adachi K, Okuwaki K, Watanabe M, Hanaoka T, Tamaki A, Kumamoto Y, Kusano C. S-1/irinotecan/oxaliplatin chemotherapy achieved a pathological complete remission in advanced pancreatic carcinoma. Clin J Gastroenterol 2025; 18:220-223. [PMID: 39503980 DOI: 10.1007/s12328-024-02055-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 10/20/2024] [Indexed: 02/01/2025]
Abstract
Chemotherapy has been developed for many years for malignancies, including advanced pancreatic cancer, downsizing the primary site, thereby enabling complete cure with the combination of conversion surgery. Pathological complete remission from operation samples was usually identified as a promising indication for a good prognosis for many carcinomas. Several case reports consisting of pathological complete remission after chemotherapy application have been reported but no case of pathological complete remission that resulted from successful extensive resection by surgery after S-1, irinotecan, and oxaliplatin (SIROX) chemotherapy. A 48-year-old male patient was hospitalized due to abdominal pain which turned out to be a 25 mm-sized advanced uncinate process of pancreatic cancer with possible duodenum invasion and hepatic metastasis. The tumor had decreased after administering 23 sessions of modified SIROX chemotherapy, and he underwent pylorus-preserving pancreaticoduodenectomy with portal vein resection. He was successfully managed with conservative treatment and discharged 12 days postoperatively despite his postoperative weakness. He had been taking S-1 pills for 6 months and until now, 3 years postoperatively, with no relapse. The final pathology reported complete tumor regression. Therefore, we emphasize the oncologic significance of chemotherapy in the uncinate process of pancreatic cancer and the potential role of conversion surgery.
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Affiliation(s)
- Ru Chen
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
- Department of Gastroenterology, Kitasato Medical Center, Kitamoto, Japan
| | - Tomohisa Iwai
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.
| | - Hiroshi Tajima
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kai Adachi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kosuke Okuwaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Masafumi Watanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Taro Hanaoka
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akihiro Tamaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Yusuke Kumamoto
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Chika Kusano
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
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Di Rito A, Grillo A, Carbonara R. Therapeutic Management in Elderly Male Breast Cancer Patients: A Scoping Review. Curr Oncol Rep 2025; 27:120-134. [PMID: 39826033 DOI: 10.1007/s11912-024-01629-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/20/2025]
Abstract
PURPOSE OF REVIEW Male breast cancer (MBC) is a rare entity which often arises in elderly people. Aim of this review is to evaluate the principal issues related to MBC in elderly, because the therapeutic management of disease is not only related to the biological behavior of the tumor, but also to the comorbidities and frailty of older population. A scoping literature review was performed on Pubmed and Cochrane Database using the following keywords: therapeutic management/ male/ breast cancer/ elderly patients. Papers published before 2000, not edited in English or French language, or not related to the main topic, were excluded. Only articles related to therapeutic issues in MBC and including more than 10 elderly (≥ 65 years) patients were selected for the qualitative outcome analysis. RECENT FINDINGS 36 papers regarding surgery, radiotherapy, systemic therapy, racial disparities and therapeutic management in retrospective series of MBC in elderly were examined in details. MBC has a different biological behavior and a poorer prognosis than female, especially in cases with positive nodes at diagnosis. Elderly MBC patients have often larger tumors in more advanced stages at the time of diagnosis compared with younger patients. In spite of the advanced tumors at presentation, older patients present often cancers with more favorable biological characteristics, but they receive less guideline-concordant curative treatments (as adequate lymph node staging or adjuvant radiation therapy) compared to women. Moreover, racial differences in treatment of older MBC were observed. Therapeutic management of MBC in elderly patients is a subject rarely addressed in literature. Our review highlighted differences in the treatment and in guidelines-concordance for elderly MBC patients. Adequate geriatric assessment and use of therapeutic schemes adapted to age and comorbidities can avoid under/overtreatment, contributing to a better standard of care in this frail population.
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Affiliation(s)
- Alessia Di Rito
- Radiotherapy Unit, Hospital Mons. A.R. Dimiccoli, Barletta, Italy.
| | - Antonietta Grillo
- Radiotherapy Unit, Azienda Ospedaliero Universitaria Policlinico Di Bari, Bari, Italy
| | - Roberta Carbonara
- Radiation Oncology Department, General Regional Hospital "F.Miulli", Acquaviva Delle Fonti, Bari, Italy
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Mattar A, Antonini M, Amorim AG, Teixeira MD, de Resende CAA, Cavalcante FP, Zerwes F, Arakelian R, Millen EDC, Brenelli FP, Frasson AL, Leite RM, Gebrim LH. Overall Survival and Economic Impact of Triple-Negative Breast Cancer in Brazilian Public Health Care: A Real-World Study. JCO Glob Oncol 2025; 11:e2400340. [PMID: 39977709 DOI: 10.1200/go-24-00340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 12/11/2024] [Accepted: 01/09/2025] [Indexed: 02/22/2025] Open
Abstract
PURPOSE Triple-negative breast cancer (TNBC) presents notable treatment difficulties, especially in the public health care systems of low- and middle-income countries where access to advanced therapies is restricted. This study investigates TNBC's clinical, epidemiologic, and economic effects on survival within Brazil's public health care system. METHODS We conducted a retrospective cohort study of patients with TNBC treated between 2010 and 2019. Overall survival (OS) rates by stage were analyzed across various patient groups, including those receiving neoadjuvant or adjuvant treatment, patients with or without complete pathologic response, Black and non-Black patients, and those treated with or without carboplatin-based therapy. Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% CIs, and annual treatment costs were calculated per stage. RESULTS Among 1,266 patients with TNBC, 710 met eligibility criteria. Kaplan-Meier analysis indicated stage II patients had a 47% lower mortality risk than stage III (HR, 0.53 [95% CI, 0.33 to 0.85]; P = .009). Patients in the adjuvant treatment group had a reduced risk (HR, 0.48 [95% CI, 0.34 to 0.69]) compared with the neoadjuvant group. Achieving complete pathologic response (pCR) greatly improved OS (HR, 0.21 [95% CI, 0.11 to 0.43]; P < .001). Black patients had better survival rates than non-Black (HR, 0.58 [95% CI, 0.40 to 0.86]; P = .006). Carboplatin use did not significantly affect OS (HR, 0.96 [95% CI, 0.65 to 1.43]; P = .857). The average monthly cost for systemic TNBC treatment increased with disease progression, from $101.87 in US dollars (USD) for stage I to $314.77 USD for stage IV second-line therapy. CONCLUSION This study provides insight into TNBC in Brazil's public health system, showing that OS decreases with disease progression but is higher among Black patients. pCR and adjuvant therapy improve survival, although costs increase significantly at advanced stages, highlighting the economic burden of late-stage TNBC management.
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Affiliation(s)
- André Mattar
- Centro de Referência da Saúde da Mulher-Hospital da Mulher, São Paulo, Brazil
- Oncoclínicas, São Paulo, Brazil
| | - Marcelo Antonini
- Hospital do Servidor Público Estadual-Francisco Morado de Oliveira, São Paulo, Brazil
| | | | | | | | | | - Felipe Zerwes
- Pontifícia Universidade Católica, Porto Alegre, Brazil
| | - Renata Arakelian
- Centro de Referência da Saúde da Mulher-Hospital da Mulher, São Paulo, Brazil
- Dasa Oncologia, São Paulo, Brazil
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Rakha EA, Quinn C, Fox S, Masannat YA, Karakatsanis A, Dixon JM. Reply to the Editor: Reassessing margin standards in breast-conserving therapy. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109504. [PMID: 39647446 DOI: 10.1016/j.ejso.2024.109504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 11/28/2024] [Indexed: 12/10/2024]
Affiliation(s)
- Emad A Rakha
- Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; Department of Pathology, Hamad Medical Corporation, Doha, Qatar.
| | - Cecily Quinn
- Irish National Breast Screening Programme and Department of Histopathology, St. Vincent's University Hospital, and School of Medicine, University College, Dublin, Ireland
| | - Stephen Fox
- Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia
| | - Yazan A Masannat
- Broomfield Breast Unit, Broomfield Hospital, Mid & South Essex NHS Trust, Chelmsford, CM1 7ET, England, UK; The London Breast Institute at Princess Grace Hospital, 42-52 Nottingham Place, London, W1U 5NY, England, UK
| | - Andreas Karakatsanis
- Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Sweden
| | - J Michael Dixon
- Edinburgh Breast Unit, and Edinburgh University and Western General Hospital Edinburgh, UK
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50
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Choi SE, Park AY, Kim GI, Jung HK, Ko KH, Kim Y. The kinetic parameters of dynamic contrast-enhanced MRI with ultrafast imaging in breast cancer patients receiving neoadjuvant chemotherapy: Prediction of pathologic complete response and correlation with histologic microvessel density. Medicine (Baltimore) 2025; 104:e40239. [PMID: 39889156 PMCID: PMC11789864 DOI: 10.1097/md.0000000000040239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 10/05/2024] [Accepted: 10/07/2024] [Indexed: 02/02/2025] Open
Abstract
Early prediction of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients can help forecast prognosis and guide decisions on adjuvant therapy. This study aimed to determine whether the kinetic parameters of dynamic contrast-enhanced MRI (DCE-MRI) with ultrafast imaging can predict pCR following NAC in breast cancer patients and whether these parameters are correlated with histologic microvessel density (MVD). In this retrospective study, 61 breast cancer patients who underwent NAC and surgery between August 2020 and 2022 were analyzed. Ultrafast and conventional DCE-MRI features, along with pathologic results, were compared between the pCR and non-pCR groups. Regression analysis was conducted to identify predictive factors for pCR. Additionally, MRI kinetic parameters were correlated with histologic MVD. Of the 61 patients, 17 (27.9%) achieved pCR. The pCR group exhibited a larger delayed washout component (P = .002) and a smaller angiovolume (P = .02) compared to the non-pCR group; however, these factors lost significance when accounting for tumor size, lymph node status, and molecular subtypes. In a subgroup analysis based on molecular subtype, a low initial enhancement value (≤362.5%) and angiovolume (≤10.3 cc) predicted pCR in human epidermal growth factor receptor 2-enriched breast cancer, with an area under the curve of 0.833. The maximum slope on ultrafast MRI was higher in the high MVD group compared to the low MVD group (P = .049). Human epidermal growth factor receptor 2-enriched breast cancer with low vascularity on DCE-MRI is more likely to achieve pCR, although MRI kinetic parameters were not independent predictors of pCR in all breast cancer subtypes. The maximum slope on ultrafast MRI was the only kinetic parameter that correlated with histologic MVD. Larger studies focused on molecular subtypes are warranted.
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Affiliation(s)
- Sung-Eun Choi
- Department of Pathology, CHA Bundang Medical Center, CHA University, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Ah Young Park
- Department of Radiology, CHA Bundang Medical Center, CHA University, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea
- Department of Radiological Sciences, University of California, Irvine, Orange, CA
| | - Gwang Il Kim
- Department of Pathology, CHA Bundang Medical Center, CHA University, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Hae Kyoung Jung
- Department of Radiology, CHA Bundang Medical Center, CHA University, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Kyung Hee Ko
- Department of Radiology, Yongin Severance Hospital, Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea
| | - Yunju Kim
- Department of Radiology, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea
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