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Lafci O, Resch D, Santonocito A, Clauser P, Helbich T, Baltzer PAT. Role of imaging based response assesment for adapting neoadjuvant systemic therapy for breast cancer: A systematic review. Eur J Radiol 2025; 187:112105. [PMID: 40252279 DOI: 10.1016/j.ejrad.2025.112105] [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: 03/06/2025] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/21/2025]
Abstract
PURPOSE The objective of this systematic review is to investigate the role of imaging in response monitoring during neoadjuvant systemic therapy (NST) for breast cancer and assess whether treatment modifications based on imaging response are implemented in clinical practice. METHODS A systematic review was conducted, analyzing five clinical practice guidelines and 147 clinical trial publications involving NST for breast cancer. The snowballing technique was employed, using a "start set" of clinical guidelines to trace relevant trials. Additionally, a PubMed search was conducted to identify trials published between 2023-2024. The review analyzed the use of imaging modalities, timing, and response criteria, and whether escalation, de-escalation, or change of treatment occurred based on imaging response. RESULTS Imaging was utilized in 81 % (119/147) of the trials, with ultrasound, MRI, and mammography being the most frequently employed modalities. Mid-treatment imaging was applied in 56 % (83/147) of the trials. However, only 15 % (22/147) of the trials implemented treatment modifications based on imaging response, highlighting the limited application of imaging response-guided therapy. No standardized imaging protocols or consistent response-guided treatment strategies were identified across the trials or clinical practice guidelines, with considerable variability in imaging methods, timing, and response criteria. CONCLUSION This systematic review underscores the critical need for standardized imaging protocols, response assessment criteria and image-guided treatment decisions. It is therefore evident that imaging for response monitoring during treatment should preferably be performed within clinical trials.
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Affiliation(s)
- Oguz Lafci
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Daphne Resch
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Ambra Santonocito
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Paola Clauser
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Thomas Helbich
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Pascal A T Baltzer
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.
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Lightowlers SV, Machin A, Woitek R, Provenzano E, Allajbeu I, Al Sarakbi W, Demiris N, Forouhi P, Gilbert FJ, Kirby AM, Towns C, Somaiah N, Coles CE. Neoadjuvant Radiotherapy and Endocrine Therapy for Oestrogen Receptor Positive Breast Cancers: The Neo-RT Feasibility Study. Clin Oncol (R Coll Radiol) 2025; 37:103669. [PMID: 39561627 DOI: 10.1016/j.clon.2024.103669] [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: 05/29/2024] [Revised: 10/07/2024] [Accepted: 10/24/2024] [Indexed: 11/21/2024]
Abstract
AIMS To establish the safety and feasibility of delivering neoadjuvant radiotherapy and endocrine therapy for oestrogen receptor-positive breast cancers with palpable size 20mm or greater, for which radiotherapy might facilitate more conservative surgery. MATERIALS AND METHODS A single-arm feasibility study was conducted. Patients received whole breast radiotherapy with or without radiotherapy to nodal areas. Dose/fractionation was 40Gy in 15 fractions over 3 weeks, with or without either a simultaneous integrated boost to 48Gy or sequential boost to the tumour bed. This was followed by endocrine treatment for 20 weeks, then surgery. The primary endpoint of the study was the proportion of patients successfully completing neoadjuvant radiotherapy and endocrine treatment followed by breast surgery. Response and toxicity endpoints including mastectomy rate, peri/postoperative complications, and pathological response were also evaluated. The primary analysis is descriptive. The study regimen would be considered feasible if more than 70% of patients completed treatment, while it might not be considered feasible if less than 50% did so. With a one-sided 5% significance level and 80% power, a maximum of 43 patients would be required to detect a rate of ≤50% vs ≥70%. RESULTS 14 patients were recruited out of the planned 43. Due to slow recruitment, particularly during the COVID-19 pandemic, the decision was made to stop the trial in October 2021. One registered patient was found to be ineligible before starting treatment. 13/13 patients (100%, 90% CI: 75.3%, 100%) who received any trial treatment successfully completed all trial treatments. The lower bound of the Clopper-Pearson (exact) 90% confidence interval was 79%, indicating that the primary endpoint would have been met if the planned recruitment had been achieved. 3/13 patients underwent mastectomy. 7/13 had more conservative surgery than had been planned at baseline. 4/13 patients experienced any peri/postoperative complication. The only acute radiotherapy toxicities reported were grade 1/2 dermatitis and grade 1 fatigue. Long-term breast outcomes were clinician assessed as none/mild at all timepoints in 12/13 patients. All tumours showed evidence of some pathological response to treatment, but none had a pathological complete response. CONCLUSION This treatment schedule is likely feasible. It is difficult to draw strong conclusions on safety/toxicity given the small numbers, but these seem in keeping with other recent reports of neoadjuvant breast radiotherapy.
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Affiliation(s)
- S V Lightowlers
- Department of Oncology, University of Cambridge School of Clinical Medicine, Cambridge, UK.
| | - A Machin
- Cambridge Clinical Trials Unit-Cancer Theme, University of Cambridge, Cambridge, UK
| | - R Woitek
- Medical Image Analysis and AI (MIAAI), Danube Private University, Krems, Austria
| | - E Provenzano
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; NIHR Cambridge Biomedical Research Centre, UK
| | - I Allajbeu
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, UK; Western Balkans University, School of Clinical Medicine, 1001, Tirana, Albania
| | | | - N Demiris
- Department of Statistics, Athens University of Economics and Business, Athens, Greece
| | - P Forouhi
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - F J Gilbert
- Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - A M Kirby
- The Royal Marsden NHS Foundation Trust, Sutton, UK
| | - C Towns
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - N Somaiah
- The Royal Marsden NHS Foundation Trust, Sutton, UK; Division of Radiotherapy and Imaging, The Institute of Cancer Research (ICR), Sutton, UK
| | - C E Coles
- Department of Oncology, University of Cambridge School of Clinical Medicine, Cambridge, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Riis MLH. The Challenges of Lobular Carcinomas from a Surgeon's Point of View. Clin Breast Cancer 2024; 24:e645-e654. [PMID: 39033066 DOI: 10.1016/j.clbc.2024.06.007] [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: 05/08/2024] [Accepted: 06/13/2024] [Indexed: 07/23/2024]
Abstract
Invasive lobular breast cancer (ILC) presents unique challenges and considerations in the realm of surgical management. Characterized by its distinct histological features, including the loss of E-cadherin expression and dys-cohesive growth pattern, ILC often poses diagnostic and therapeutic dilemmas for clinicians. This abstract explores the surgical landscape of ILC, focusing on its epidemiology, clinical presentation, diagnostic modalities, and surgical interventions. Emphasizing the importance of individualized treatment strategies, this narrative delves into the nuances of surgical decision-making, including the role of breast-conserving surgery versus mastectomy, axillary staging, and the significance of margin status. Additionally, advancements in surgical techniques, such as oncoplastic approaches and sentinel lymph node biopsy, are examined in the context of optimizing oncologic outcomes and preserving cosmesis. Through a comprehensive review of current literature and clinical guidelines, this overview aims to provide a nuanced understanding of the surgical considerations inherent to the management of invasive lobular breast cancer.
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Affiliation(s)
- Margit L H Riis
- Department of Breast and Endocrine Surgery, Oslo University Hospital, Oslo, Norway.
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Han X, Li H, Zhou SY, Dong SS, Zhang GL. Clinical efficacy of combined goserelin and anastrozole in neoadjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer. Discov Oncol 2024; 15:554. [PMID: 39397134 PMCID: PMC11471739 DOI: 10.1007/s12672-024-01418-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 10/01/2024] [Indexed: 10/15/2024] Open
Abstract
OBJECTIVE The objective of this study is to assess the efficacy and safety of combining goserelin with anastrozole in neoadjuvant endocrine therapy (NET) for patients diagnosed with premenopausal breast cancer. METHODS A retrospective analysis was conducted on the clinicopathological data of 34 patients diagnosed with premenopausal breast cancer who underwent NET in the Department of Breast Surgery at Baotou Cancer Hospital between March 2016 and December 2019. Additionally, the feasibility of using goserelin combined with anastrozole for premenopausal endocrine therapy was assessed. RESULTS The duration of NET ranged from 6 to 72 months, with a mean of 22.5 months and a median of 18 months. In patients with progressive disease, endocrine therapy was assessed over a period of 6 to 18 months, with a mean of 13.1 months and a median of 13 months. Among the 28 patients assessed, 12 (42.86%) were found to have stable disease, subsequently receiving chemotherapy. Of these, seven patients demonstrated good compliance, and 5 achieved a pathological complete response. Including the 2 patients who responded favorably to NET alone, a total of 7 patients attained a pathological complete response. Additionally, 16 patients achieved complete cell cycle arrest following treatment. A significant correlation was observed between the clinical efficacy assessment and the pathological assessment of NET (P < 0.05). CONCLUSION Although NET was safe for patients diagnosed with premenopausal breast cancer, it should not be considered in isolation from chemotherapy. Transitioning to chemotherapy in a timely manner can significantly enhance treatment outcomes. The duration of NET should be guided by clinical assessment rather than being constrained by a predetermined time frame.
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Affiliation(s)
- Xu Han
- Department of Breast Surgery, Baotou Cancer Hospital of Inner Mongolia, No.18 Tuanjie Street, Qingshan District, Baotou, 014030, Inner Mongolia, China
| | - Hui Li
- Department of Breast Surgery, Baotou Cancer Hospital of Inner Mongolia, No.18 Tuanjie Street, Qingshan District, Baotou, 014030, Inner Mongolia, China
| | - Shui-Ying Zhou
- Department of Breast Surgery, Baotou Cancer Hospital of Inner Mongolia, No.18 Tuanjie Street, Qingshan District, Baotou, 014030, Inner Mongolia, China
| | - Sha-Sha Dong
- Department of Breast Surgery, Baotou Cancer Hospital of Inner Mongolia, No.18 Tuanjie Street, Qingshan District, Baotou, 014030, Inner Mongolia, China
| | - Gang-Ling Zhang
- Department of Breast Surgery, Baotou Cancer Hospital of Inner Mongolia, No.18 Tuanjie Street, Qingshan District, Baotou, 014030, Inner Mongolia, China.
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Chae H, Sim SH, Kwon Y, Lee EG, Han JH, Jung SY, Lee S, Kang HS, Kim YJ, Kim TH, Lee KS. Neoadjuvant Chemotherapy with Concurrent Letrozole for Estrogen Receptor-Positive and HER2-Negative Breast Cancer: An Open-Label, Single-Center, Nonrandomized Phase II Study (NeoCHAI). Cancers (Basel) 2024; 16:3122. [PMID: 39335094 PMCID: PMC11430478 DOI: 10.3390/cancers16183122] [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: 07/30/2024] [Revised: 09/03/2024] [Accepted: 09/06/2024] [Indexed: 09/30/2024] Open
Abstract
The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon's minimax two-stage design; a pCR rate > 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33-63), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo-endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.
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Affiliation(s)
- Heejung Chae
- Department of Internal Medicine, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
- Cancer Data Center, National Cancer Control Institute, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Sung Hoon Sim
- Department of Internal Medicine, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
- Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Youngmi Kwon
- Department of Pathology, National Cancer Center, Hospital, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Eun-Gyeong Lee
- Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Jai Hong Han
- Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - So-Youn Jung
- Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
- Division of Clinical Research, Research Institute, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Seeyoun Lee
- Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Han-Sung Kang
- Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Yeon-Joo Kim
- Center for Proton Therapy, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Tae Hyun Kim
- Center for Proton Therapy, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
| | - Keun Seok Lee
- Department of Internal Medicine, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea
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Brett B, Savva C, Mirshekar-Syahkal B, Hill M, Douek M, Copson E, Cutress R. Surgical outcomes of neoadjuvant endocrine treatment in early breast cancer: meta-analysis. BJS Open 2024; 8:zrae100. [PMID: 39423044 PMCID: PMC11488384 DOI: 10.1093/bjsopen/zrae100] [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: 02/02/2024] [Revised: 05/29/2024] [Accepted: 07/15/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Neoadjuvant endocrine therapy presents an important downstaging option with lower toxicity than neoadjuvant chemotherapy in oestrogen receptor (ER)-positive early breast cancer. Meta-analysis of the effects of neoadjuvant endocrine therapy on surgical outcomes across randomized clinical trials (RCTs) and cohort studies has not previously been performed. METHODS A systematic review and meta-analysis was performed to evaluate the effect of neoadjuvant endocrine therapy on surgical outcomes (PROSPERO (international prospective register of systematic reviews, 2020)) compared with surgery followed by adjuvant endocrine therapy. PubMed and EMBASE were searched to identify RCT and cohort studies between 1946 and 27 March 2024. Two independent reviewers manually screened the identified records and extracted the data. Risk of bias was assessed using the Cochrane Collaboration tools and random-effects meta-analysis was done with ReviewManager. RESULTS The search identified 2390 articles eligible for screening. The review included 20 studies (12 cohort and 8 RCTs); 19 were included in the meta-analysis with a total of 6382 patients. Overall, neoadjuvant endocrine therapy was associated with a lower mastectomy rate compared with surgery first (risk ratio (RR) 0.53, 95% c.i. 0.44 to 0.64). Subgroup analysis showed similar improvement in the mastectomy rate in the neoadjuvant endocrine therapy group versus control group irrespective of study type (RCT: RR 0.58, 95% c.i. 0.50 to 0.66; cohorts: RR 0.48, 95% c.i. 0.33 to 0.70). There was no difference in the mastectomy rate by duration of neoadjuvant endocrine therapy (more than 4 months: RR 0.57, 95% c.i. 0.42 to 0.78; 4 months or less than 4 months: RR 0.52, 95% c.i. 0.43 to 0.64). Most of the studies were characterized by moderate-quality evidence with significant heterogeneity. CONCLUSION Neoadjuvant endocrine therapy is associated with a reduction in mastectomy rate. Given the moderate methodological quality of previous studies, further RCTs are required. REGISTRATION ID CRD42020209257.
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Affiliation(s)
- Beatrice Brett
- Cancer Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton, Southampton, UK
| | - Constantinos Savva
- Cancer Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton, Southampton, UK
| | | | - Martyn Hill
- Nuffield Department of Surgical Sciences, University of Oxford and John Radcliffe Hospital, Oxford, UK
| | - Michael Douek
- Nuffield Department of Surgical Sciences, University of Oxford and John Radcliffe Hospital, Oxford, UK
| | - Ellen Copson
- Cancer Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton, Southampton, UK
| | - Ramsey Cutress
- Cancer Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton, Southampton, UK
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Xing D, Lv Y, Sun B, Chu T, Bao Q, Zhang H. Develop and Validate a Nomogram Combining Contrast-Enhanced Spectral Mammography Deep Learning with Clinical-Pathological Features to Predict Neoadjuvant Chemotherapy Response in Patients with ER-Positive/HER2-Negative Breast Cancer. Acad Radiol 2024; 31:3524-3534. [PMID: 38641451 DOI: 10.1016/j.acra.2024.03.035] [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: 01/18/2024] [Revised: 03/23/2024] [Accepted: 03/26/2024] [Indexed: 04/21/2024]
Abstract
RATIONALE AND OBJECTIVES To develop and validate a nomogram that combines contrast-enhanced spectral mammography (CESM) deep learning with clinical-pathological features to predict neoadjuvant chemotherapy (NAC) response (either low Miller Payne (MP-L) grades 1-2 or high MP (MP-H) grades 3-5) in patients with ER-positive/HER2-negative breast cancer. MATERIALS AND METHODS In this retrospective study, 265 breast cancer patients were randomly allocated into training and test sets (used for models training and testing, respectively) at a 4:1 ratio. Deep learning models, based on the pre-trained ResNet34 model and initially fine-tuned for identifying breast cancer, were trained using low-energy and subtracted CESM images. The predicted results served as deep learning features for the deep learning-based model. Clinical-pathological features, including age, progesterone receptor (PR) status, estrogen receptor (ER) status, Ki67 expression levels, and neutrophil-to-lymphocyte ratio, were used for the clinical model. All these features contributed to the nomogram. Feature selection was performed through univariate analysis. Logistic regression models were developed and chosen using a stepwise selection method. The deep learning-based and clinical models, along with the nomogram, were evaluated using precision-recall curves, receiver operating characteristic (ROC) curves, specificity, recall, accuracy, negative predictive value, positive predictive value (PPV), balanced accuracy, F1-score, and decision curve analysis (DCA). RESULTS The nomogram demonstrated considerable predictive ability, with higher area under the ROC curve (0.95, P < 0.05), accuracy (0.94), specificity (0.98), PPV (0.89), and precision (0.89) compared to the deep learning-based and clinical models. In DCA, the nomogram showed substantial clinical value in assisting breast cancer treatment decisions, exhibiting a higher net benefit than the other models. CONCLUSION The nomogram, integrating CESM deep learning with clinical-pathological features, proved valuable for predicting NAC response in patients with ER-positive/HER2-negative breast cancer. Nomogram outperformed deep learning-based and clinical models.
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Affiliation(s)
- Dong Xing
- Department of Radiology,Yantai Yuhuangding Hospital, Yantai, Shandong 264000 China
| | - Yongbin Lv
- Department of Radiology,Yantai Yuhuangding Hospital, Yantai, Shandong 264000 China
| | - Bolin Sun
- Department of Interventional Therapy, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, China
| | - Tongpeng Chu
- Department of Radiology,Yantai Yuhuangding Hospital, Yantai, Shandong 264000 China; Big Data and Artificial Intelligence Lab, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, China
| | - Qianhao Bao
- Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250300, China
| | - Han Zhang
- Department of Radiology,Yantai Yuhuangding Hospital, Yantai, Shandong 264000 China.
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Bischoff H, Espié M, Petit T. Neoadjuvant Therapy: Current Landscape and Future Horizons for ER-Positive/HER2-Negative and Triple-Negative Early Breast Cancer. Curr Treat Options Oncol 2024; 25:1210-1224. [PMID: 39145854 PMCID: PMC11416407 DOI: 10.1007/s11864-024-01251-y] [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: 07/25/2024] [Indexed: 08/16/2024]
Abstract
OPINION STATEMENT Navigating the complex landscape of breast cancer treatment involves distinct strategies for luminal and triple-negative subtypes. While neoadjuvant chemotherapy historically dominates the approach for aggressive triple-negative tumors, recent evidence highlights the transformative impact of immunotherapy, alongside chemotherapy, in reshaping treatment paradigms. In luminal cancers, endocrine therapy, notably aromatase inhibitors, demonstrates promising outcomes in postmenopausal patients with low-grade luminal A tumors. However, integrating targeted therapies like CDK4/6 inhibitors in neoadjuvant setting remains inconclusive. Identifying predictive factors for treatment response, especially in luminal tumors, poses a challenge, emphasizing the necessity for ongoing research. A multidisciplinary approach, tailored to individual patient profiles, is crucial for maximizing efficacy while minimizing toxicity. As we strive to optimize breast cancer management, a comprehensive understanding of the distinct characteristics and treatment implications of luminal and triple-negative subtypes, including the transformative role of immunotherapy, is essential for informed decision-making and personalized care.
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Affiliation(s)
- Hervé Bischoff
- Medical Oncology Department, Institut de Cancérologie Strasbourg Europe, ICANS, 17 Rue Albert Calmette, 67033, Strasbourg, France.
| | - Marc Espié
- Medical Oncology Department, Hôpital Saint Louis, Paris, France
| | - Thierry Petit
- Medical Oncology Department, Institut de Cancérologie Strasbourg Europe, ICANS, 17 Rue Albert Calmette, 67033, Strasbourg, France
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Fjermeros K, Ghannoum S, Geisler SB, Bhargava S, Tahiri A, Klajic J, Lüders T, Fongård M, Nawaz MS, Bosnjak-Olsen T, Buvarp UCE, Rosenskiold AKJ, Nguyen NT, Sletbak TT, Seyedzadeh M, Selsås K, Porojnicu AC, Skjerven HK, Hovda T, Sahlberg KK, Torland LA, Lyngra M, Hammarström CL, Hönigsperger EB, Noone JC, Mathiassen S, Hurtado A, Goel S, Koff A, Tekpli X, Kristensen VN, Geisler J. The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer. Future Oncol 2024; 20:2457-2466. [PMID: 39073142 PMCID: PMC11520546 DOI: 10.1080/14796694.2024.2377531] [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: 05/13/2024] [Accepted: 07/04/2024] [Indexed: 07/30/2024] Open
Abstract
Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.Trial registration number: NCT05163106 (ClinicalTrials.gov).
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Affiliation(s)
- Kamilla Fjermeros
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Salim Ghannoum
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | | | - Sameer Bhargava
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
- Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway
| | - Andliena Tahiri
- Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital, Lørenskog, Norway
| | - Jovana Klajic
- Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital, Lørenskog, Norway
| | - Torben Lüders
- Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital, Lørenskog, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Marie Fongård
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Meh Sameen Nawaz
- Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital, Lørenskog, Norway
- Department of Health and Exercise, School of Health Sciences, Kristiania University College, Oslo, Norway
| | | | | | | | - Nam Thi Nguyen
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | | | | | - Knut Selsås
- Department of Endocrine & Breast Surgery, Akershus University Hospital, Lørenskog, Norway
| | | | - Helle Kristine Skjerven
- Department of Breast & Endocrine Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | - Tone Hovda
- Department of Radiology, Drammen Hospital, Vestre Viken Hospital Trust, Norway
| | - Kristine Kleivi Sahlberg
- Department of Research & Innovation, Vestre Viken Hospital Trust, Drammen, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Lilly Anne Torland
- Department of Research & Innovation, Vestre Viken Hospital Trust, Drammen, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Marianne Lyngra
- Department of Pathology, Akershus University Hospital, Lørenskog, Norway
| | | | | | | | - Silje Mathiassen
- Department of Pathology, Akershus University Hospital, Lørenskog, Norway
| | - Antoni Hurtado
- Functional Genomics group & Molecular Pathology Unit, Centro de Investigación del Cáncer (CSIC-Universidad de Salamanca), Campus Universitario Miguel de Unamuno s/n. 37007, Salamanca, Spain
| | - Shom Goel
- Peter MacCallum Cancer Centre, Australia & The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
| | - Andrew Koff
- Program in Molecular Biology, Memorial Sloan Kettering Cancer Center & Weill Cornell Medical College, New York, NY USA
| | - Xavier Tekpli
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Vessela N. Kristensen
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Jürgen Geisler
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
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10
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Vaz SC, Woll JPP, Cardoso F, Groheux D, Cook GJR, Ulaner GA, Jacene H, Rubio IT, Schoones JW, Peeters MJV, Poortmans P, Mann RM, Graff SL, Dibble EH, de Geus-Oei LF. Joint EANM-SNMMI guideline on the role of 2-[ 18F]FDG PET/CT in no special type breast cancer : (endorsed by the ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). Eur J Nucl Med Mol Imaging 2024; 51:2706-2732. [PMID: 38740576 PMCID: PMC11224102 DOI: 10.1007/s00259-024-06696-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 03/20/2024] [Indexed: 05/16/2024]
Abstract
INTRODUCTION There is much literature about the role of 2-[18F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. PURPOSE To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). METHODS Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[18F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. RESULTS Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[18F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[18F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[18F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[18F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. CONCLUSION 2-[18F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.
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Affiliation(s)
- Sofia C Vaz
- Nuclear Medicine-Radiopharmacology, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal.
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
| | | | - Fatima Cardoso
- Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal
| | - David Groheux
- Nuclear Medicine Department, Saint-Louis Hospital, Paris, France
- University Paris-Diderot, INSERM U976, Paris, France
- Centre d'Imagerie Radio-Isotopique (CIRI), La Rochelle, France
| | - Gary J R Cook
- Department of Cancer Imaging, King's College London, London, UK
- King's College London and Guy's & St Thomas' PET Centre, London, UK
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Gary A Ulaner
- Molecular Imaging and Therapy, Hoag Family Cancer Institute, Newport Beach, CA, USA
- University of Southern California, Los Angeles, CA, USA
| | - Heather Jacene
- Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Isabel T Rubio
- Breast Surgical Oncology, Clinica Universidad de Navarra, Madrid, Cancer Center Clinica Universidad de Navarra, Navarra, Spain
| | - Jan W Schoones
- Directorate of Research Policy, Leiden University Medical Center, Leiden, The Netherlands
| | - Marie-Jeanne Vrancken Peeters
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Philip Poortmans
- Department of Radiation Oncology, Iridium Netwerk, Antwerp, Belgium
- University of Antwerp, Wilrijk, Antwerp, Belgium
| | - Ritse M Mann
- Radiology Department, RadboudUMC, Nijmegen, The Netherlands
| | - Stephanie L Graff
- Lifespan Cancer Institute, Providence, Rhode Island, USA
- Legorreta Cancer Center at Brown University, Providence, Rhode Island, USA
| | - Elizabeth H Dibble
- Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
- Biomedical Photonic Imaging Group, University of Twente, Enschede, The Netherlands.
- Department of Radiation Science & Technology, Technical University of Delft, Delft, The Netherlands.
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11
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Xu P, Luo W, Hu J, Ma X, Hao Q, Hui W, Zhou Z, Lin S, Wang M, Wu H, Dai Z, Kang H. Favorable outcome of neoadjuvant endocrine treatment than surgery-first in female HR-positive/HER2-negative breast cancer patients-A NCDB analysis (2010-2016). Cancer Med 2024; 13:e7244. [PMID: 38859692 PMCID: PMC11165171 DOI: 10.1002/cam4.7244] [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: 12/11/2023] [Revised: 03/03/2024] [Accepted: 04/27/2024] [Indexed: 06/12/2024] Open
Abstract
PURPOSE To assess the efficacy of neoadjuvant endocrine therapy in female HR-positive/HER2-negative breast cancer patients. DATA AND METHODS We identified female patients aged ≥18 years with cT1-4N0-XM0, HR(+), and HER2(-) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery-first," while those who received NET before surgery were classified as "NET." Propensity score-matching, Cox proportional-hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. RESULTS Among 432,387 cases, 2914 NET patients and 2914 surgery-first patients were matched. Compared with the surgery-first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery-first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery-first vs. NET: HR 2.17, 95% CI: 1.93-2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(-), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). CONCLUSION NET may be a more effective treatment procedure than surgery-first in female HR-positive/HER2-negative, non-metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher-level evidence-based data.
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Affiliation(s)
- Peng Xu
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Wen Luo
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Jingjing Hu
- Massachusetts General Cancer CenterBostonMassachusettsUSA
| | - Xiaobin Ma
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Qian Hao
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Wentao Hui
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Zhangjian Zhou
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Shuai Lin
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Meng Wang
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Hao Wu
- Department of Biophysics, School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to DiseasesXi'an Jiaotong University Health Science CenterXi'anShaanxiChina
| | - Zhijun Dai
- Department of Breast SurgeryThe First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina
| | - Huafeng Kang
- The Comprehensive Breast Care CenterThe Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
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12
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van de Loo ME, Andour L, van Heesewijk AE, Oosterkamp HM, Liefers GJ, Straver ME. Neoadjuvant endocrine treatment in hormone receptor-positive breast cancer: Does it result in more breast-conserving surgery? Breast Cancer Res Treat 2024; 205:5-16. [PMID: 38265568 DOI: 10.1007/s10549-023-07222-5] [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: 06/30/2023] [Accepted: 12/10/2023] [Indexed: 01/25/2024]
Abstract
BACKGROUND Patients with locally advanced endocrine positive tumors who will not benefit from chemotherapy can be treated by either primary surgery or neoadjuvant endocrine therapy (NET). How often does NET result in breast-conserving surgery (BCS)? METHODS We conducted a literature search in PubMed and Embase, to identify articles on surgical treatment after NET. RESULTS In 19 studies the pathological complete response (pCR) rate was reported after NET; an overall pCR rate of 1% was found. Compared with neoadjuvant chemotherapy (NCT), the BCS rate was significantly higher after NET (OR 0.60; 95% CI, 0.51-0.69; P < 0.00001). The surgical conversion rate was reported in eight studies [4-75.9%], with a mean of 30.2%. CONCLUSION This review found that one out of three patients becomes eligible for BCS after treatment with NET.
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Affiliation(s)
- Merel E van de Loo
- Department of Surgery, Medical Center Haaglanden, The Hague, The Netherlands
| | - Layla Andour
- Department of Surgery, Medical Center Haaglanden, The Hague, The Netherlands
| | | | | | - Gerrit-Jan Liefers
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Marieke E Straver
- Department of Surgery, Medical Center Haaglanden, The Hague, The Netherlands.
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13
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Hoshina H, Sakatani T, Kawamoto Y, Ohashi R, Takei H. Cytomorphological Disparities in Invasive Breast Cancer Cells following Neoadjuvant Endocrine Therapy and Chemotherapy. Pathobiology 2024; 91:288-298. [PMID: 38447546 PMCID: PMC11309077 DOI: 10.1159/000538227] [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: 10/04/2023] [Accepted: 03/04/2024] [Indexed: 03/08/2024] Open
Abstract
INTRODUCTION Neoadjuvant endocrine therapy (NAE) offers a breast-conserving surgery rate and clinical response rate similar to those of neoadjuvant chemotherapy (NAC), while presenting fewer adverse events and lower pathological complete response rates. The assessment of pathological response determines degenerative changes and predicts the prognosis of breast cancer treated with NAC. This study clarified the degenerative changes occurring in breast cancer following NAE. METHODS Our study encompassed two groups: NAE, consisting of 15 patients, and NAC, comprising 18 patients. Tissue samples were obtained from core needle biopsies and surgeries. Nuclear and cell areas were calculated using Autocell analysis. Furthermore, we assessed markers associated with microtubule depolymerization (KIF2A) and initiators of apoptosis (caspase-9). RESULTS In the NAC group, we observed significant increases in both cytoplasmic and cell areas. These changes in cytoplasm and cells were notably more pronounced in the NAC group compared to the NAE group. After treatment, KIF2A exhibited a decrease, with the magnitude of change being greater in the NET group than in the NAC group. However, no discernible differences were found in caspase-9 expression between the two groups. CONCLUSION Our findings indicate that NAE induces condensation in cancer cells via cell cycle arrest or apoptosis. Conversely, NAC leads to cell enlargement due to the absence of microtubule depolymerization. These discrepancies underscore the importance of accounting for these distinctions when establishing criteria for evaluating pathological responses.
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Affiliation(s)
- Hideko Hoshina
- Department of Breast Surgery and Oncology, Nippon Medical School, Tokyo, Japan,
| | - Takashi Sakatani
- Department of Diagnostic Pathology, Nippon Medical School Hospital, Tokyo, Japan
| | - Yoko Kawamoto
- Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan
| | - Ryuji Ohashi
- Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan
| | - Hiroyuki Takei
- Department of Breast Surgery and Oncology, Nippon Medical School, Tokyo, Japan
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14
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Cantini L, Trapani D, Guidi L, Boscolo Bielo L, Scafetta R, Koziej M, Vidal L, Saini KS, Curigliano G. Neoadjuvant therapy in hormone Receptor-Positive/HER2-Negative breast cancer. Cancer Treat Rev 2024; 123:102669. [PMID: 38141462 DOI: 10.1016/j.ctrv.2023.102669] [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: 09/20/2023] [Revised: 12/05/2023] [Accepted: 12/07/2023] [Indexed: 12/25/2023]
Abstract
Neoadjuvant therapy is commonly used in patients with locally advanced or inoperable breast cancer (BC). Neoadjuvant chemotherapy (NACT) represents an established treatment modality able to downstage tumours, facilitate breast-conserving surgery, yet also achieve considerable pathologic complete response (pCR) rates in HER2-positive and triple-negative BC. For patients with HR+/HER2- BC, the choice between NACT and neoadjuvant endocrine therapy (NET) is still based on clinical and pathological features and not guided by biomarkers of defined clinical utility, differently from the adjuvant setting where gene-expression signatures have been widely adopted to drive decision-making. In this review, we summarize the evidence supporting the choice of NACT vs NET in HR+/HER2- BC, discussing the issues surrounding clinical trial design and proper selection of patients for every treatment. It is time to question the binary paradigm of responder vs non-responders as well as the "one size fits all" approach in luminal BC, supporting the utilization of continuous endpoints and the adoption of tissue and plasma-based biomarkers at multiple timepoints. This will eventually unleash the full potential of neoadjuvant therapy which is to modulate patient treatment based on treatment sensitivity and surgical outcomes. We also reviewed the current landscape of neoadjuvant studies for HR+/HER2- BC, focusing on antibody-drug conjugates (ADCs) and immunotherapy combinations. Finally, we proposed a roadmap for future neoadjuvant approaches in HR+/HER2- BC, which should be based on a staggered biomarker-driven treatment selection aiming at impacting long-term relevant endpoints.
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Affiliation(s)
| | - Dario Trapani
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy; Division of New Drugs and Early Drug Development, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy
| | - Lorenzo Guidi
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy; Division of New Drugs and Early Drug Development, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy
| | - Luca Boscolo Bielo
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy; Division of New Drugs and Early Drug Development, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy
| | - Roberta Scafetta
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy; Division of New Drugs and Early Drug Development, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy; Department of medical oncology, Campus Bio-Medico, University of Rome, Rome, Italy
| | | | | | | | - Giuseppe Curigliano
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy; Division of New Drugs and Early Drug Development, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy.
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15
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Paiva CE, Zonta MPM, Granero RC, Guimarães VS, Pimenta LM, Teixeira GR, Paiva BSR. The Magee 3 Equation Predicts Favorable Pathologic Response to Neoadjuvant Endocrine Therapy in Breast Cancer Patients. Cancers (Basel) 2024; 16:339. [PMID: 38254828 PMCID: PMC10813970 DOI: 10.3390/cancers16020339] [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: 09/25/2023] [Revised: 10/27/2023] [Accepted: 11/01/2023] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Breast cancer (BC) remains a significant health care challenge, and treatment approaches continue to evolve. Among these, neoadjuvant endocrine therapy (NET) has gained prominence, particularly for postmenopausal, hormone-receptor positive, HER2-negative (HR+/HER2-) BC patients. Despite this, a significant gap exists in identifying patients who stand to benefit from NET. The objective of this study was to assess whether Magee equations (MEs) could serve as predictors of response to NET. METHODS This retrospective study included adult patients with invasive BC who underwent NET followed by curative surgery. Assessment of sociodemographic, clinical, and tumor-related variables was conducted. The ME1, ME2, ME3, and ME mean were analyzed to explore their predictive role for NET response. Receiver operating characteristic (ROC) curves were employed, along with the determination of optimal cutoff points. Logistic regression models were utilized to identify the most significant predictors of pathological response. RESULTS Among the 75 female participants, the mean age was 69.4 years, with the majority being postmenopausal (n = 72, 96%) and having an ECOG-PS of 0/1 (n = 63, 84%). Most patients were classified as luminal A (n = 41, 54.7%). ME3 emerged as a promising predictor, boasting an AUC of 0.734, with sensitivity of 90.62% and specificity of 57.50% when the threshold was ≤ 19.97. In univariate analysis, clinical staging (p = 0.002), molecular subtype (p = 0.001), and ME3 (continuous = 0.001, original 3-tier: p = 0.013, new 2-tier: <0.001) categories exhibited significant associations with pathological response. In the multivariate model, clinical staging and new 2-tier ME3 (<20 vs. ≥20) were included as significant variables. CONCLUSIONS Patients with ME3 < 20 have a higher likelihood of presenting a pathological response, offering a cost-effective alternative tool to Oncotype DX. Larger future studies with a prospective design are awaited to confirm our findings.
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Affiliation(s)
- Carlos Eduardo Paiva
- Department of Clinical Oncology, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil;
| | - Maria Paola Montesso Zonta
- Barretos School of Health Sciences Dr. Paulo Prata—FACISB, Barretos 14785-002, SP, Brazil; (M.P.M.Z.); (R.C.G.); (G.R.T.)
| | - Rafaela Carvalho Granero
- Barretos School of Health Sciences Dr. Paulo Prata—FACISB, Barretos 14785-002, SP, Brazil; (M.P.M.Z.); (R.C.G.); (G.R.T.)
| | - Vitor Souza Guimarães
- Department of Clinical Oncology, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil;
| | - Layla Melo Pimenta
- Department of Pathology, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil;
| | - Gustavo Ramos Teixeira
- Barretos School of Health Sciences Dr. Paulo Prata—FACISB, Barretos 14785-002, SP, Brazil; (M.P.M.Z.); (R.C.G.); (G.R.T.)
- Department of Pathology, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil;
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16
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Paiva CE, Silva ATF, Oliveira IDS, Guimarães VS, Lacerda DC, Teixeira GR, Watanabe AHU, Onari N, Paiva BSR, de Oliveira-Junior I, Marques MMC, Maia YCDP. A Research Protocol for a Phase II Single-Arm Clinical Trial Assessing the Feasibility and Efficacy of Neoadjuvant Anastrozole in Patients With Luminal Breast Cancer and Low Proliferative Index: The ANNE Trial. Cancer Control 2024; 31:10732748241272463. [PMID: 39140157 PMCID: PMC11325316 DOI: 10.1177/10732748241272463] [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: 01/19/2024] [Revised: 06/26/2024] [Accepted: 07/09/2024] [Indexed: 08/15/2024] Open
Abstract
INTRODUCTION Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited. AIMS This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month). METHODS Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.
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Affiliation(s)
- Carlos Eduardo Paiva
- Deparment of Clinical Oncology, Barretos Cancer Hospital, Barretos-SP, Brazil
- Palliative Care and Quality of Life Research Group (GPQual), Barretos Cancer Hospital, Barretos-SP, Brazil
| | - Alinne Tatiane Faria Silva
- Nutrition and Molecular Biology Research Group, School of Medicine, Federal University of Uberlandia, Uberlandia, Brazil
- Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Brazil
| | - Izabella da Silva Oliveira
- Palliative Care and Quality of Life Research Group (GPQual), Barretos Cancer Hospital, Barretos-SP, Brazil
| | - Vitor Souza Guimarães
- Palliative Care and Quality of Life Research Group (GPQual), Barretos Cancer Hospital, Barretos-SP, Brazil
| | | | - Gustavo Ramos Teixeira
- Department of Pathology, Barretos Cancer Hospital, Barretos-SP, Brazil
- Barretos School of Health Sciences Dr. Paulo Prata – FACISB, Barretos-SP, Brazil
| | | | - Nilton Onari
- Department of Breast Radiology, Barretos Cancer Hospital, Barretos-SP, Brazil
| | | | | | | | - Yara Cristina de Paiva Maia
- Nutrition and Molecular Biology Research Group, School of Medicine, Federal University of Uberlandia, Uberlandia, Brazil
- Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Brazil
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17
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Zhan H, Fineberg S, Podany P, Zeng J, Wang Y, Harigopal M, Singh K. Pathological response in mucinous carcinoma of breast after neoadjuvant therapy - a multi-institutional study. Hum Pathol 2023; 142:15-19. [PMID: 37972873 DOI: 10.1016/j.humpath.2023.10.002] [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: 07/03/2023] [Revised: 09/05/2023] [Accepted: 10/20/2023] [Indexed: 11/19/2023]
Abstract
Although mucinous carcinoma (MC) is considered a favorable histologic subtype of invasive breast cancer (BC), a subset of MC is managed with neoadjuvant therapy (NAT). The clinical and pathologic features of MC following NAT are not well characterized. The aim of this study is to characterize pathologic response in patients with MC treated with NAT, including neoadjuvant endocrine therapy (NET), neoadjuvant chemotherapy (NCT), and Herceptin-targeted NCT (H-NCT). We conducted a retrospective cohort study of 28 patients with MC who received preoperative adjuvant therapy followed by resection from three institutions between 2010 and 2020. Demographic and clinical information were retrieved from the medical records. Pathologic review of the post NAT resection specimens was performed including tumor grading, tumor size, staging, residual tumor cellularity, estrogen receptor (ER) and HER2 status. Nine (32 %) patients with ER+/HER2- MC received NET, 8 (29 %) ER+/HER2- MC were treated with NCT only and 11 (39 %) HER2+ MC received HER2-targeted NCT (H-NCT). The HER2+ MC patients were younger (45 vs. 64 years; p = 0.006). The HER2+ MC were of higher grade (p = 0.03) and more likely to be multifocal (p = 0.008). Only 2 of 28 (7 %) MC (both HER2+) showed complete pathologic response with residual acellular mucin pools. Persistent mass-forming mucin pools were present in 26 (93 %) cases. The residual tumor cellularity was markedly reduced (≤5 %) in H-NCT treated MC (11/11, 100 %), followed by NET group (6/9, 67 %) and NCT only group (4/8, 50 %) (p = 0.011). Similarly, a higher rate of pathologic response (pCR/RCB-I) was observed in H-NCT (7/11, 64 %), followed by NET group (5/9, 56 %), and NCT only group (1/7, 13 %) (p = 0.053). Post-therapy, all HER2+ MC were smaller than 2 cm and ypT size was significantly smaller in H-NCT group (11/11, 100 %) versus combined NET (5/9, 55 %) and NCT only groups (4/8, 50 %) (p = 0.029). We conclude that ER-/HER2+ and ER+/HER2-mucinous carcinomas of the breast show robust pathological response to neoadjuvant HER2 targeted and endocrine therapy, respectively. Our findings suggest that MC may show good response to endocrine therapy.
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Affiliation(s)
- Haiying Zhan
- Yale University School of Medicine, Department of Pathology, New Haven, CT, USA
| | - Susan Fineberg
- Montefiore Medical Center, Department of Pathology, New York, NY, USA
| | - Peter Podany
- Yale University School of Medicine, Department of Pathology, New Haven, CT, USA
| | - Jennifer Zeng
- Icahn School of Medicine at Mount Sinai, Department of Pathology, New York, NY, USA
| | - Yihong Wang
- Brown University Rhode Island Hospital, Department of Pathology, RI, USA
| | - Malini Harigopal
- Yale University School of Medicine, Department of Pathology, New Haven, CT, USA
| | - Kamaljeet Singh
- Brown University Women and Infants Hospital of Rhode Island, Department of Pathology, RI, USA.
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18
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Jeong H, Kim SB. Neoadjuvant endocrine therapy in ER-positive breast cancer: evolution, indication, and tailored treatment strategy. Ther Adv Med Oncol 2023; 15:17588359231200457. [PMID: 37786536 PMCID: PMC10541763 DOI: 10.1177/17588359231200457] [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: 11/27/2022] [Accepted: 08/25/2023] [Indexed: 10/04/2023] Open
Abstract
In recent years, endocrine therapy (ET), an effective systemic treatment for the management of estrogen receptor (ER)-positive breast cancers, has regained interest as a neoadjuvant therapy based on evidence that ET can fulfill the aim of neoadjuvant systemic treatment for tumor shrinkage as well as elucidate important clinical information on endocrine sensitivity that enables the prognostication of patients. Moreover, neoadjuvant endocrine therapy (NET) potentially provides an opportunity for early assessment of the clinical efficacy of novel agents. Furthermore, recently reported trials have generated evidence for a more tailored approach for perioperative management of ER-positive breast cancer using clinical and molecular biomarkers, and this has provided a rationale that enables the broadening of clinical indications for NET. This review discusses the current evidence for NET, the evolution of NET trials, clinical indications, and NET-based treatment strategies.
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Affiliation(s)
- Hyehyun Jeong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Bae Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea
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Litton JK, Regan MM, Pusztai L, Rugo HS, Tolaney SM, Garrett-Mayer E, Amiri-Kordestani L, Basho RK, Best AF, Boileau JF, Denkert C, Foster JC, Harbeck N, Jacene HA, King TA, Mason G, O'Sullivan CC, Prowell TM, Richardson AL, Sepulveda KA, Smith ML, Tjoe JA, Turashvili G, Woodward WA, Butler LP, Schwartz EI, Korde LA. Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP. J Clin Oncol 2023; 41:4433-4442. [PMID: 37433103 PMCID: PMC10522109 DOI: 10.1200/jco.23.00435] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 04/25/2023] [Accepted: 06/06/2023] [Indexed: 07/13/2023] Open
Abstract
PURPOSE The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007 and updated in 2021 (STEEP 2.0), provide standardized definitions of adjuvant breast cancer (BC) end points. STEEP 2.0 identified a need to separately address end points for neoadjuvant clinical trials. The multidisciplinary NeoSTEEP working group of experts was convened to critically evaluate and align neoadjuvant BC trial end points. METHODS The NeoSTEEP working group concentrated on neoadjuvant systemic therapy end points in clinical trials with efficacy outcomes-both pathologic and time-to-event survival end points-particularly for registrational intent. Special considerations for subtypes and therapeutic approaches, imaging, nodal staging at surgery, bilateral and multifocal diseases, correlative tissue collection, and US Food and Drug Administration regulatory considerations were contemplated. RESULTS The working group recommends a preferred definition of pathologic complete response (pCR) as the absence of residual invasive cancer in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0 per AJCC staging). Residual cancer burden should be a secondary end point to facilitate future assessment of its utility. Alternative end points are needed for hormone receptor-positive disease. Time-to-event survival end point definitions should pay particular attention to the measurement starting point. Trials should include end points originating at random assignment (event-free survival and overall survival) to capture presurgery progression and deaths as events. Secondary end points adapted from STEEP 2.0, which are defined from starting at curative-intent surgery, may also be appropriate. Specification and standardization of biopsy protocols, imaging, and pathologic nodal evaluation are also crucial. CONCLUSION End points in addition to pCR should be selected on the basis of clinical and biologic aspects of the tumor and the therapeutic agent investigated. Consistent prespecified definitions and interventions are paramount for clinically meaningful trial results and cross-trial comparison.
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Affiliation(s)
- Jennifer K. Litton
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Meredith M. Regan
- Division of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
| | - Lajos Pusztai
- Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT
| | - Hope S. Rugo
- University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
| | - Sara M. Tolaney
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | | | | | - Reva K. Basho
- The Lawrence J. Ellison Institute for Transformative Medicine, Los Angeles, CA
| | - Ana F. Best
- Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD
| | | | - Carsten Denkert
- Institute of Pathology, Philipps University Marburg and University Hospital Marburg (UKGM), Marburg, Germany
| | - Jared C. Foster
- Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD
| | - Nadia Harbeck
- The Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Munich, LMU University Hospital, Munich, Germany
| | | | - Tari A. King
- Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA
| | - Ginny Mason
- The Inflammatory Breast Cancer Research Foundation, Broadway, VA
| | | | - Tatiana M. Prowell
- US Food and Drug Administration, Silver Spring, MD
- Women's Malignancies Disease Group, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD
| | | | | | | | - Judy A. Tjoe
- Division of Breast Surgery, Department of Surgery, Novant Health, Greensboro, NC
| | - Gulisa Turashvili
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA
| | - Wendy A. Woodward
- Department of Breast Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Elena I. Schwartz
- Coordinating Center for Clinical Trials, National Cancer Institute, Rockville, MD
| | - Larissa A. Korde
- Cancer Therapy and Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD
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Groheux D, Ulaner GA, Hindie E. Breast cancer: treatment response assessment with FDG-PET/CT in the neoadjuvant and in the metastatic setting. Clin Transl Imaging 2023; 11:439-452. [DOI: 10.1007/s40336-023-00584-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 07/10/2023] [Indexed: 01/03/2025]
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Zaborowski AM, Wong SM. Neoadjuvant systemic therapy for breast cancer. Br J Surg 2023; 110:765-772. [PMID: 37104057 PMCID: PMC10683941 DOI: 10.1093/bjs/znad103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/02/2023] [Indexed: 04/28/2023]
Affiliation(s)
| | - Stephanie M Wong
- Department of Surgery and Oncology, McGill University Medical School, Montreal, Quebec, Canada
- Segal Cancer Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada
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Chen S, Saeed AFUH, Liu Q, Jiang Q, Xu H, Xiao GG, Rao L, Duo Y. Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther 2023; 8:207. [PMID: 37211559 DOI: 10.1038/s41392-023-01452-1] [Citation(s) in RCA: 593] [Impact Index Per Article: 296.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 03/06/2023] [Accepted: 04/26/2023] [Indexed: 05/23/2023] Open
Abstract
Macrophages exist in various tissues, several body cavities, and around mucosal surfaces and are a vital part of the innate immune system for host defense against many pathogens and cancers. Macrophages possess binary M1/M2 macrophage polarization settings, which perform a central role in an array of immune tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about macrophage signaling and immune modulation are yet to be uncovered. In addition, the clinical importance of tumor-associated macrophages is becoming more widely recognized as significant progress has been made in understanding their biology. Moreover, they are an integral part of the tumor microenvironment, playing a part in the regulation of a wide variety of processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, and resistance to chemotherapeutic and checkpoint blockade immunotherapies. Herein, we discuss immune regulation in macrophage polarization and signaling, mechanical stresses and modulation, metabolic signaling pathways, mitochondrial and transcriptional, and epigenetic regulation. Furthermore, we have broadly extended the understanding of macrophages in extracellular traps and the essential roles of autophagy and aging in regulating macrophage functions. Moreover, we discussed recent advances in macrophages-mediated immune regulation of autoimmune diseases and tumorigenesis. Lastly, we discussed targeted macrophage therapy to portray prospective targets for therapeutic strategies in health and diseases.
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Affiliation(s)
- Shanze Chen
- Department of Respiratory Diseases and Critic Care Unit, Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China
| | - Abdullah F U H Saeed
- Department of Cancer Biology, Beckman Research Institute of City of Hope National Medical Center, Los Angeles, CA, 91010, USA
| | - Quan Liu
- Department of Laboratory Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen University, Shenzhen, 518052, China
| | - Qiong Jiang
- Department of Respiratory Diseases and Critic Care Unit, Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China
| | - Haizhao Xu
- Department of Respiratory Diseases and Critic Care Unit, Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China
- Department of Respiratory, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China
| | - Gary Guishan Xiao
- State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian, China.
| | - Lang Rao
- Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
| | - Yanhong Duo
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
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23
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Alfaris I, Asselah J, Aziz H, Bouganim N, Mousavi N. The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer. Curr Atheroscler Rep 2023; 25:145-154. [PMID: 36848014 DOI: 10.1007/s11883-023-01085-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/22/2023] [Indexed: 03/01/2023]
Abstract
PURPOSE OF REVIEW Cardiovascular disease accounts for up to 10% of all-cause mortality in women with a diagnosis of breast cancer, and the causes for this are multifaceted. Many women at risk of or with a diagnosis of breast cancer are on endocrine-modulating therapies. It is therefore important to understand the effect of hormone therapies on cardiovascular outcomes in breast cancer patients to mitigate against any adverse effects and to identify those most at risk so that they can be proactively managed. Here we discuss the pathophysiology of these agents, their effect on the cardiovascular system, and the latest evidence on their cardiovascular risks association. RECENT FINDINGS Tamoxifen appears to be cardioprotective during treatment but not over the longer term, while the effect of AIs on cardiovascular outcomes remains controversial. Heart failure outcomes remain understudied, and the cardiovascular effects of gonadotrophin-releasing hormone agonists (GNRHa) in women need further research, especially since data from men with prostate cancer have indicated an increased risk of cardiac events in GNRHa users. There remains a need for a greater understanding of the effects of hormone therapies on cardiovascular outcomes in breast cancer patients. Further areas of research in this area include developing evidence to better define the optimal preventive and screening methods for cardiovascular effects and the risk factors for patients on hormonal therapies.
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Affiliation(s)
- Ibrahim Alfaris
- Division of Cardiology, Department of Medicine, McGill University Health Center, Montreal, Canada.
| | - Jamil Asselah
- Department of Oncology, McGill University Health Center, Montreal, Canada
| | - Haya Aziz
- Division of Cardiology, Department of Medicine, McGill University Health Center, Montreal, Canada
| | - Nathaniel Bouganim
- Department of Oncology, McGill University Health Center, Montreal, Canada
| | - Negareh Mousavi
- Division of Cardiology, Department of Medicine, McGill University Health Center, Montreal, Canada
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24
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Hunt KK, Suman VJ, Wingate HF, Leitch AM, Unzeitig G, Boughey JC, Meric-Bernstam F, Ellis MJ, Olson J. Local-Regional Recurrence After Neoadjuvant Endocrine Therapy: Data from ACOSOG Z1031 (Alliance), a Randomized Phase 2 Neoadjuvant Comparison Between Letrozole, Anastrozole, and Exemestane for Postmenopausal Women with Estrogen Receptor-Positive Clinical Stage 2 or 3 Breast Cancer. Ann Surg Oncol 2023; 30:2111-2118. [PMID: 36653664 PMCID: PMC10373661 DOI: 10.1245/s10434-022-12972-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 10/26/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND The ACOSOG Z1031 trial addressed the ability of three neoadjuvant aromatase inhibitors (NAIs) to reduce residual disease (cohort A) and to assess whether switching to neoadjuvant chemotherapy (NCT) after 4 weeks of receiving NAI with Ki67 greater than 10% increases pathologic complete response (pCR) in postmenopausal women with estrogen receptor-enriched (Allred score 6-8) breast cancer (BC). METHODS The study enrolled 622 women with clinical stage 2 or 3 estrogen receptor-positive (ER+) BC. Cohort A comprised 377 patients, and cohort B had 245 patients. The analysis cohort consisted of 509 patients after exclusion of patients who did not meet the trial eligibility criteria, switched to NCT or surgery due to 4-week Ki67 greater than 10%, or withdrew before surgery. Distribution of time to local-regional recurrence (LRR) was estimated using the competing-risk approach, in which distant recurrence and second primaries were considered to be competing-risk events. Patients who died without LRR, distant recurrence, or a second primary were censored at the last evaluation. RESULTS Of the 509 patients, 342 (67.2%) had breast-conserving surgery (BCS). Of 221 patients thought to require mastectomy at presentation, 50% were able to have BCS. Five (1%) patients had no residual disease in the breast or nodes at surgery. Among 382 women alive at this writing, 90% have been followed longer than 5 years. The 5-year cumulative incidence rate for LRR is estimated to be 1.53% (95% confidence interval 0.7-3.0%). CONCLUSIONS Rarely does NAI result in pCR for patients with stage 2 or 3 ER+ BC. However, a significant proportion will have downstaged to allow for BCS. Local-regional recurrence after surgery is uncommon (1.5% at 5 years), supporting the use of BCS after NAI.
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Affiliation(s)
- Kelly K Hunt
- Breast Surgical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA.
| | - Vera J Suman
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA
| | - Hannah F Wingate
- Breast Surgical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA
| | - A Marilyn Leitch
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | | | | | | | - Matthew J Ellis
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
| | - John Olson
- Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA
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25
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Taylor C, Meisel J, Foreman AJ, Russell C, Bandyopadhyay D, Deng X, Floyd L, Zelnak A, Bear H, O'Regan R. Using Oncotype DX breast recurrence score® assay to define the role of neoadjuvant endocrine therapy in early-stage hormone receptor-positive breast cancer. Breast Cancer Res Treat 2023; 199:91-98. [PMID: 36897465 PMCID: PMC10147793 DOI: 10.1007/s10549-023-06890-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 02/08/2023] [Indexed: 03/11/2023]
Abstract
PURPOSE The role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need. METHODS We assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay. RESULTS We observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy, suggesting that a subgroup of women with a RS 0-25 may omit chemotherapy without compromising outcomes. CONCLUSION These data suggest that Recurrence Score® (RS) results may serve as a useful tool in treatment decision-making in the neoadjuvant setting.
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Affiliation(s)
| | | | | | | | | | - Xiaoyan Deng
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA
| | | | | | - Harry Bear
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA
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Sirico M, Virga A, Conte B, Urbini M, Ulivi P, Gianni C, Merloni F, Palleschi M, Gasperoni M, Curcio A, Saha D, Buono G, Muñoz M, De Giorgi U, Schettini F. Neoadjuvant endocrine therapy for luminal breast tumors: State of the art, challenges and future perspectives. Crit Rev Oncol Hematol 2023; 181:103900. [PMID: 36565894 DOI: 10.1016/j.critrevonc.2022.103900] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
Neoadjuvant endocrine treatment (NET) associates to satisfactory rates of breast conservative surgery and conversions from inoperable to operable hormone receptor-positive (HR+)/HER2-negative breast cancer (BC), with less toxicities than neoadjuvant chemotherapy (NACT) and similar outcomes. Hence, it has been proposed as a logical alternative to NACT in patients with HR+/HER2- BC candidate to a neoadjuvant approach. Nevertheless, potential barriers to the widespread use of NET include the heterogeneous nature of patient response coupled with the long duration needed to achieve a clinical response. However, interest in NET has significantly increased in the last decade, owing to more in-depth investigation of several biomarkers for a more adequate patient selection and on-treatment benefit monitoring, such as PEPI score, Ki67 and genomic assays. This review is intended to describe the state-of-the-art regarding NET, its future perspectives and potential integration with molecular biomarkers for the optimal selection of patients, regimen and duration of (neo)adjuvant treatments.
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Affiliation(s)
- Marianna Sirico
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Alessandra Virga
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Benedetta Conte
- Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
| | - Milena Urbini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Paola Ulivi
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Caterina Gianni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Filippo Merloni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Michela Palleschi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Marco Gasperoni
- Breast Surgery Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Annalisa Curcio
- Breast Surgery Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Debjani Saha
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Giuseppe Buono
- Department of Breast and Thoracic Oncology, National Cancer Institute, Fondazione G. Pascale, Naples, Italy
| | - Montserrat Muñoz
- Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Ugo De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Francesco Schettini
- Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain
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27
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Qin Q, Han X, Li H, Zhou SY, Wang CH, Zhang GL. The effect of prolonged neoadjuvant endocrine therapy on the efficacy of treatment with breast cancer. Technol Health Care 2023; 31:2059-2071. [PMID: 37393441 DOI: 10.3233/thc-220443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/03/2023]
Abstract
BACKGROUND At present, there is no consensus on the required duration of neoadjuvant endocrine therapy (NET), yet there is no consistent conclusion on the factors influencing the efficacy of treatment with breast cancer after prolonged treatment. OBJECTIVE To explore the effect of prolonged NET on the efficacy of patients with breast cancer and analyze the factors influencing the efficacy of treatment with breast cancer after the treatment duration is prolonged. METHODS The case histories of 51 patients who were diagnosed with breast cancer and received NET in our hospital from September 2017 to December 2021 were retrospectively analyzed. All patients received NET for over 12 months. The clinical efficacy and tumor size changes after treatment for six months and 12 months were compared, and the factors influencing the efficacy of treatment with breast cancer after patients' treatment duration was prolonged were analyzed. RESULTS (1) Among the 51 patients, the objective remission rate (ORR) of NET, at T = 6 months was 21.6%, and the average tumor size was 15.52 ± 7.30 mm. The ORR of the NET at T = 12 months was 52.9%, and the average tumor size was 13.79 ± 7.43 mm. (2) After the treatment duration was prolonged, the clinical ORRs of patients with estrogen receptor (ER) (+) and progesterone receptor (PR) (+) were significantly higher than that of patients with ER (+) and PR (-) and patients with ER (-) and PR (+), which was (P < 0.05). (3) There was no significant difference between the patients' axillary lymph node status and the Ki67 expression before treatment and the clinical ORR after prolonged treatment, which was (P> 0.05). CONCLUSIONS (1) Prolonging the NET duration for patients with breast cancer can improve their clinical ORR and further reduce the tumor size, but patients' conditions should be closely monitored during the treatment process to prevent the progression of disease due to drug resistance. (2) The expression state of ER or PR may be used as a factor influencing the efficacy of treatment with breast cancer after prolonged treatment. (3) There was no significant effect on the patients' axillary lymph node status and the Ki67 expression before treatment on the clinical efficacy after prolonged treatment.
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Affiliation(s)
- Qin Qin
- Department of Breast Surgery II, BaoTou Tumor Hospital, Baotou, China
- Maizidian Community Health Service Center, Beijing, China
| | - Xu Han
- Department of Breast Surgery II, BaoTou Tumor Hospital, Baotou, China
| | - Hui Li
- Department of Breast Surgery II, BaoTou Tumor Hospital, Baotou, China
| | - Shui-Ying Zhou
- Department of Breast Surgery II, BaoTou Tumor Hospital, Baotou, China
| | - Cai-Hong Wang
- The Operating Room, BaoTou Tumor Hospital, Baotou, China
| | - Gang-Ling Zhang
- Department of Breast Surgery II, BaoTou Tumor Hospital, Baotou, China
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Martínez-Pérez C, Turnbull AK, Kay C, Dixon JM. Neoadjuvant endocrine therapy in postmenopausal women with HR+/HER2- breast cancer. Expert Rev Anticancer Ther 2023; 23:67-86. [PMID: 36633402 DOI: 10.1080/14737140.2023.2162043] [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: 10/14/2022] [Accepted: 12/20/2022] [Indexed: 01/13/2023]
Abstract
INTRODUCTION While endocrine therapy is the standard-of-care adjuvant treatment for hormone receptor-positive (HR+) breast cancers, there is also extensive evidence for the role of pre-operative (or neoadjuvant) endocrine therapy (NET) in HR+ postmenopausal women. AREAS COVERED We conducted a thorough review of the published literature, to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET. We describe the importance of on-treatment assessment of response, the different predictors available (including Ki67, PEPI score, and molecular signatures) and the research opportunities the pre-operative setting offers. We also summarize recent combination trials and discuss how the COVID-19 pandemic led to increases in NET use for safe management of cases with deferred surgery and adjuvant treatments. EXPERT OPINION NET represents a safe and effective tool for the management of postmenopausal women with HR+/HER2- breast cancer, enabling disease downstaging and a wider range of surgical options. Aromatase inhibitors are the preferred NET, with evidence suggesting that longer regimens might yield optimal results. However, NET remains currently underutilised in many territories and institutions. Further validation of predictors for treatment response and benefit is needed to help standardise and fully exploit the potential of NET in the clinic.
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Affiliation(s)
- Carlos Martínez-Pérez
- Translational Oncology Research Group, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
- Edinburgh Breast Cancer Now Research Team, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
| | - Arran K Turnbull
- Translational Oncology Research Group, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
- Edinburgh Breast Cancer Now Research Team, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
| | - Charlene Kay
- Translational Oncology Research Group, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
- Edinburgh Breast Cancer Now Research Team, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
| | - J Michael Dixon
- Translational Oncology Research Group, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
- Edinburgh Breast Cancer Now Research Team, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland
- Edinburgh Breast Unit, Western General Hospital, Edinburgh, Scotland
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29
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Gan Y, Lo Y, Makower D, Kleer C, Lu J, Fineberg S. EZH2 Protein Expression in Estrogen Receptor Positive Invasive Breast Cancer Treated With Neoadjuvant Endocrine Therapy: An Exploratory Study of Association With Tumor Response. Appl Immunohistochem Mol Morphol 2022; 30:614-622. [PMID: 36048167 PMCID: PMC9577480 DOI: 10.1097/pai.0000000000001055] [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: 04/27/2022] [Accepted: 08/04/2022] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Neoadjuvant endocrine therapy (NET) can be used to treat estrogen receptor positive (ER+) invasive breast cancer (IBC). Tumors with Ki67>10% after 2 to 4 weeks of NET are considered resistant to endocrine therapy. Enhancer of Zeste Homolog 2 (EZH2) is a targetable oncoprotein and overexpression in ER+ IBC has been linked to resistance to endocrine therapy. We examined whether EZH2 expression levels in ER+ IBC could be used to predict response to NET. MATERIALS AND METHODS We retrospectively identified 46 patients with localized ER+ HER2/neu negative IBC treated with a minimum of 4 weeks of NET. We quantified EZH2 nuclear expression in pretherapy core biopsies using a score that included intensity and percent of cells staining. Ki67 was evaluated in both pretherapy core biopsies and posttherapy tumor resections and scored according to the guidelines of the International Ki67 Working Groups, with a global weighted score. Ki67≤10% after NET was considered endocrine responsive. Logistic regression analysis was performed to determine the association between EZH2 expression and response to NET. RESULTS We found significant associations of tumor grade ( P =0.011), pretherapy Ki67 ( P =0.003), and EZH2 ( P <0.001), with response to NET. On logistic regression adjusted for tumor grade and pretherapy Ki67, increased EZH2 scores were associated with decreased odds of endocrine responsiveness, defined as posttreatment Ki67≤10% (odds ratio=0.976, 95% CI, 0.956 to 0.997; P =0.026). In addition, with EZH2 score in the model, associations of tumor grade and pretreatment Ki67 with posttreatment Ki67≤10% response to NET became not significant. CONCLUSIONS Our results suggest that EZH2 might be a useful biomarker to predict response to NET.
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Affiliation(s)
- Yujun Gan
- Department of Pathology, Montefiore Medical Center and The Albert Einstein College of Medicine 111 East 210th Street Bronx NY 10467
- Department of Pathology, Dartmouth Hitchcock Medical Center, 2 Medical Center Drive, Lebanon New Hampshire 03756
| | - Yungtai Lo
- Department of Pathology, Montefiore Medical Center and The Albert Einstein College of Medicine 111 East 210th Street Bronx NY 10467
- Department of Epidemiology and Population Health Montefiore Medical Center and The Albert Einstein College of Medicine, 111 East 210 Street Bronx NY 10467
| | - Della Makower
- Department of Medical Oncology, Montefiore Medical Center and The Albert Einstein College of Medicine, 111 East 210 Street Bronx NY 10467
| | - Celina Kleer
- Department of Pathology, University of Michigan Medical School and The Rogel Cancer Center, 1500 E Medical Center Dr., Ann Arbor MI 48109
| | - Jinyu Lu
- Department of Medical Oncology, Montefiore Medical Center and The Albert Einstein College of Medicine, 111 East 210 Street Bronx NY 10467
| | - Susan Fineberg
- Department of Pathology, Montefiore Medical Center and The Albert Einstein College of Medicine 111 East 210th Street Bronx NY 10467
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Abstract
There is growing interest in neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 -negative (HR + HER2-) breast cancer. Expanding the use of genomic assays demonstrates that many patients with HR + HER2-breast cancer do not benefit from chemotherapy, leading to growing interest in NET as a less toxic alternative. Although NET's ability to downsize breast tumors and achieve breast conservation is well-known, axillary surgery algorithms are not well-defined. Here we review primary endocrine therapy, the landmark NET clinical trials, and management of residual nodal disease following NET.
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Affiliation(s)
- Anna Weiss
- Division of Breast Surgery, Brigham and Women's Hospital, Dana-Farber/Brigham Cancer Center, Harvard Medical School, 450 Brookline Avenue, YC 1220, Boston, MA, USA
| | - Tari A King
- Division of Breast Surgery, Brigham and Women's Hospital, Dana-Farber/Brigham Cancer Center, Harvard Medical School, 450 Brookline Avenue, YC 1220, Boston, MA, USA.
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31
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Spring LM, Bar Y, Isakoff SJ. The Evolving Role of Neoadjuvant Therapy for Operable Breast Cancer. J Natl Compr Canc Netw 2022; 20:723-734. [PMID: 35714678 DOI: 10.6004/jnccn.2022.7016] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/28/2022] [Indexed: 11/17/2022]
Abstract
The role of neoadjuvant therapy (NAT) for localized breast cancer has evolved tremendously over the past several years. Currently, NAT is the preferred option for high-risk early triple-negative (TN) and HER2-positive (HER2+) breast cancers and is indicated for some estrogen receptor-positive (ER+) breast cancers. In addition to traditional absolute indications for NAT, relative indications such as the assessment of outcomes at the time of surgery and guidance of treatment escalation and de-escalation have greatly evolved in recent years. Pathologic complete response (pCR) and the Residual Cancer Burden (RCB) index are highly prognostic for disease recurrence and survival, mainly in patients with TN or HER2+ disease. Furthermore, post-NAT escalation strategies have been shown to improve long-term outcomes of patients who do not achieve pCR. Additionally, by allowing the direct assessment of drug effect on the tumor, the neoadjuvant setting has become an attractive setting for the exploration of novel agents and the identification of predictive biomarkers. Neoadjuvant trial design has also evolved, using adaptive treatment approaches that enable treatment de-escalation or escalation based on response. However, despite multiple practice-changing neoadjuvant trials and the addition of various new agents to the neoadjuvant setting for early breast cancer, many key questions remain. For example, patient selection for neoadjuvant immunotherapy in TN breast cancer, de-escalation methods in HER2+ breast cancer, and the use of gene expression profiles to guide NAT recommendations in ER+ breast cancer. This article reviews the current approach for NAT in localized breast cancer as well as evolving NAT strategies, the key remaining challenges, and the ongoing work in the field.
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Affiliation(s)
- Laura M Spring
- Massachusetts General Hospital Cancer Center, and.,Harvard Medical School, Boston, Massachusetts
| | - Yael Bar
- Massachusetts General Hospital Cancer Center, and
| | - Steven J Isakoff
- Massachusetts General Hospital Cancer Center, and.,Harvard Medical School, Boston, Massachusetts
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32
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Jacobs CF, Soesan M, Sonke GS. Concurrent chemo-endocrine treatment for early hormone-positive breast cancer: a no-go??? Breast Cancer Res Treat 2022; 192:485-489. [PMID: 35132502 DOI: 10.1007/s10549-021-06505-z] [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: 10/06/2021] [Accepted: 12/29/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE Endocrine therapy is one of the cornerstones of early breast cancer treatment. While this medication could be initiated on the day of diagnosis, it is often postponed until after completion of surgery, radiotherapy, and chemotherapy. This practice is based on preclinical data suggesting an antagonistic effect between endocrine therapy and cytostatic agents, and on the interpretation of clinical trials comparing concurrent versus sequential use of tamoxifen and chemotherapy. These clinical trials, however, have never shown a statistically significant difference in overall survival or disease-free survival and focused on tamoxifen rather than aromatase inhibitors. Nevertheless, sequentially administered endocrine and chemotherapy have become standard of care worldwide. RESULTS We performed a literature review and conclude that concurrent endocrine chemotherapy is at least as effective as sequential treatment. In fact, higher response rates have been observed in trials with aromatase inhibitors rather than tamoxifen in a neoadjuvant setting. CONCLUSION We encourage breast cancer oncologists to re-consider concurrent endocrine chemotherapy as a possible treatment strategy enabling early start of potentially curative endocrine treatment.
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Affiliation(s)
- C F Jacobs
- Department of Medical Oncology, The Netherlands Cancer Institute, NKI-AvL, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - M Soesan
- Department of Medical Oncology, The Netherlands Cancer Institute, NKI-AvL, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
| | - G S Sonke
- Department of Medical Oncology, The Netherlands Cancer Institute, NKI-AvL, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
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33
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Impact of the COVID-19 pandemic on breast surgery and breast reconstruction in a Japanese university hospital setting. Arch Plast Surg 2022; 49:132-136. [PMID: 35086324 PMCID: PMC8795639 DOI: 10.5999/aps.2021.01438] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Accepted: 09/30/2021] [Indexed: 11/08/2022] Open
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34
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Karsono R, Haryono SJ, Karsono B, Harahap WA, Pratiwi Y, Aryandono T. ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer. BMC Cancer 2021; 21:1348. [PMID: 34930150 PMCID: PMC8686387 DOI: 10.1186/s12885-021-09083-x] [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: 06/04/2020] [Accepted: 12/05/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer. METHODS This retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples. RESULTS The percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05-3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days). CONCLUSION The ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.
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Affiliation(s)
- Ramadhan Karsono
- Department of Surgical Oncology, Dharmais Hospital-National Cancer Center, Jakarta, Indonesia.
| | - Samuel J Haryono
- Department of Surgical Oncology, Dharmais Hospital-National Cancer Center, Jakarta, Indonesia
| | - Bambang Karsono
- Department of Hematology and Medical Oncology, Dharmais Hospital-National Cancer Center, Jakarta, Indonesia
| | - Wirsma Arif Harahap
- Surgical Oncology Division, Faculty of Medicine Universitas Andalas/Dr. M Djamil General Hospital Padang, West Sumatera, Indonesia
| | - Yulia Pratiwi
- Functional Medical Staff of Surgical Oncology Department, Dharmais Hospital-National Cancer Center, Jakarta, Indonesia
| | - Teguh Aryandono
- Department of Surgery, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
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35
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Hadar T, Koretz M, Nawass M, Allweis TM. Innovative Standards in Surgery of the Breast after Neoadjuvant Systemic Therapy. Breast Care (Basel) 2021; 16:590-597. [PMID: 35087362 PMCID: PMC8739938 DOI: 10.1159/000520051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 09/29/2021] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND The goal of neoadjuvant systemic therapy (NST) in breast cancer is to downstage tumors and downgrade treatment. Indications are constantly evolving. These changes raise practical questions for planning of surgery after NST. SUMMARY In this review we discuss current evolving aspects of surgery of the breast after NST. Breast-conserving surgery (BCS) eligibility increases after NST - both neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy. Adequate margin width in NST and upfront surgery are similar - "no tumor on ink" for invasive cancer. Oncoplastic breast surgery after NST is feasible - both for BCS and mastectomy with reconstruction. There is increasing interest in the possibility of omitting surgery in patients with a complete response to NAC. Several trials are being conducted in aim of achieving acceptable prediction of pathological complete response, by combination of imaging and percutaneous biopsy of the tumor bed, as well as assessing the safety of such an approach. KEY MESSAGES Surgery of the breast after NST should be determined not only according to biologic and anatomic parameters at diagnosis, but is dynamic, and must be tailored according to the response to therapy. The omission of surgery in exceptional responders after NAC is being explored.
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Affiliation(s)
- Tal Hadar
- Department of Breast Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
| | - Michael Koretz
- Department of Breast Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Mahmood Nawass
- Department of Breast Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Tanir M. Allweis
- Department of Breast Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
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36
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Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM, Senn HJ, Winer EP, Gnant M. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol 2021; 32:1216-1235. [PMID: 34242744 PMCID: PMC9906308 DOI: 10.1016/j.annonc.2021.06.023] [Citation(s) in RCA: 462] [Impact Index Per Article: 115.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/22/2021] [Accepted: 06/27/2021] [Indexed: 12/12/2022] Open
Abstract
The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.
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Affiliation(s)
- H J Burstein
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
| | - G Curigliano
- European Institute of Oncology, University of Milan, Milan, Italy.
| | | | - W P Weber
- University of Basel, Basel, Switzerland
| | | | - M M Regan
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - H J Senn
- St. Gallen Oncology Conferences (Foundation SONK), St. Gallen, Switzerland
| | - E P Winer
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - M Gnant
- Medical University of Vienna, Vienna, Austria
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37
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Battisti NML, Joshi K, Nasser MS, Ring A. Systemic therapy for older patients with early breast cancer. Cancer Treat Rev 2021; 100:102292. [PMID: 34536728 DOI: 10.1016/j.ctrv.2021.102292] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 09/07/2021] [Indexed: 12/16/2022]
Abstract
Over a third of breast cancers are diagnosed in patients ≥70 years. With the ageing of the population, the number of older breast cancer patients will continue to rise. Older patients are under-represented in clinical studies underpinning breast cancer therapy, and frequently do not receive guideline-concordant care. This review outlines the evidence on the efficacy and the safety of systemic treatment options for the management of early-stage breast cancer (EBC) in older adults and identifies where critical data gaps exist. Chemotherapy is beneficial for older patients with oestrogen receptor (ER)-negative EBC, whilst the benefit for those with ER-positive disease is less certain. Careful consideration should be given to the side-effect profile of the treatment regimen chosen, owing to the risks of myelosuppression and cardiac damage, as well as toxicities, such as neuropathy, that may impact independence. The impact of chemotherapy on quality of life (QOL) outcomes appears significant but reversible in this population. Gene expression profiling, benefit and chemotherapy toxicity prediction tools integrating global health considerations hold promise to better inform chemotherapy decisions in this population. Benefits on targeted anti-human epidermal growth factor receptor 2 (HER2) agents is maintained in older EBC patients with a favourable safety profile. Endocrine therapy including aromatase inhibitors is the standard of care in this population, and extended treatment decisions should consider effects on bone health and life expectancy. More trials recruiting older adults with pragmatic designs and meaningful endpoints for this population are warranted to better inform systemic treatment decisions and discussion with patients.
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Affiliation(s)
- Nicolò Matteo Luca Battisti
- Department of Medicine - Breast Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom; Breast Cancer Research Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London SM2 5NG, United Kingdom.
| | - Kroopa Joshi
- Department of Medicine - Breast Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom.
| | - Mariam Syeda Nasser
- Department of Medicine - Breast Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom.
| | - Alistair Ring
- Department of Medicine - Breast Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom.
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38
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Merheb D, Dib G, Zerdan MB, Nakib CE, Alame S, Assi HI. Drug-Induced Peripheral Neuropathy: Diagnosis and Management. Curr Cancer Drug Targets 2021; 22:49-76. [PMID: 34288840 DOI: 10.2174/1568009621666210720142542] [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: 01/28/2021] [Revised: 05/07/2021] [Accepted: 05/21/2021] [Indexed: 01/09/2023]
Abstract
Peripheral neuropathy comes in all shapes and forms and is a disorder which is found in the peripheral nervous system. It can have an acute or chronic onset depending on the multitude of pathophysiologic mechanisms involving different parts of nerve fibers. A systematic approach is highly beneficial when it comes to cost-effective diagnosis. More than 30 causes of peripheral neuropathy exist ranging from systemic and auto-immune diseases, vitamin deficiencies, viral infections, diabetes, etc. One of the major causes of peripheral neuropathy is drug induced disease, which can be split into peripheral neuropathy caused by chemotherapy or by other medications. This review deals with the latest causes of drug induced peripheral neuropathy, the population involved, the findings on physical examination and various workups needed and how to manage each case.
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Affiliation(s)
- Diala Merheb
- Department of Internal Medicine, Saint George Hospital University Medical Center, Beirut, Lebanon
| | - Georgette Dib
- Department of Internal Medicine, Division of Neurology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maroun Bou Zerdan
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Clara El Nakib
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Saada Alame
- Department of Pediatrics, Clemenceau Medical Center, Faculty of Medical Sciences, Lebanese University, Beirut,, Lebanon
| | - Hazem I Assi
- Department of Internal Medicine Naef K. Basile Cancer Institute American University of Beirut Medical Center Riad El Solh 1107 2020 Beirut, Lebanon
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39
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Jagosky M, Tan AR. Combination of Pertuzumab and Trastuzumab in the Treatment of HER2-Positive Early Breast Cancer: A Review of the Emerging Clinical Data. BREAST CANCER-TARGETS AND THERAPY 2021; 13:393-407. [PMID: 34163239 PMCID: PMC8213954 DOI: 10.2147/bctt.s176514] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 03/23/2021] [Indexed: 01/03/2023]
Abstract
Human epidermal growth factor receptor type 2 (HER2) is a relevant and effective target in breast cancer. The development of monoclonal antibodies against HER2 has revolutionized the treatment of HER2-positive breast cancer. The humanized monoclonal antibody, trastuzumab, was the first in its class to be widely adopted. It was initially studied in the metastatic setting and then in the treatment of early-stage disease, demonstrating significant improvement in overall survival in both settings. The addition of pertuzumab further improved upon results achieved with trastuzumab and chemotherapy, specifically extending overall survival in patients with metastatic disease, lessening the risk of recurrence when used in the adjuvant setting, and improving pathologic complete response rate when utilized in the neoadjuvant setting. In this article, we review the studies that support the use of HER2-directed monoclonal antibodies in early-stage breast cancer both in the adjuvant and neoadjuvant settings and focus on the success of dual HER2-targeted therapy achieved with the combination of trastuzumab and pertuzumab. A newer way to administer these agents, specifically the subcutaneous formulation of pertuzumab and trastuzumab with recombinant human hyaluronidase, will also be discussed.
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Affiliation(s)
- Megan Jagosky
- Department of Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Antoinette R Tan
- Department of Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
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40
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The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment. Cancers (Basel) 2021; 13:cancers13112538. [PMID: 34064183 PMCID: PMC8196711 DOI: 10.3390/cancers13112538] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 05/16/2021] [Accepted: 05/19/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary The treatment of breast cancer has evolved considerably over the last two decades, leading toward individualized disease management. Hormone-sensitive breast cancers constitute the vast majority of cases and endocrine therapy is the mainstay of their treatment. On the other hand, neoadjuvant or pre-surgical treatments provide a number of advantages for tumor management. In this review we will discuss the existing evidence on neoadjuvant endocrine therapy, as well as its possible future indications. Abstract Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.
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41
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Badr NM, Spooner D, Steven J, Stevens A, Shaaban AM. Morphological and molecular changes following neoadjuvant endocrine therapy of oestrogen receptor-positive breast cancer: implications for clinical practice. Histopathology 2021; 79:47-56. [PMID: 33423290 DOI: 10.1111/his.14331] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 12/31/2020] [Accepted: 01/06/2021] [Indexed: 11/27/2022]
Abstract
AIMS Neoadjuvant endocrine therapy (NAET) is used in the management of oestrogen receptor (ER)-positive breast cancer. The optimal method for histological assessment of response and the effect of NAET on the tumour morphology, grade and molecular profile remain unclear. The aim of this study is to investigate the NAET effect on tumour type, grade and molecular profile by analysing a well-characterised cohort of breast cancer samples in a single large UK tertiary referral centre, and to provide guidance on the pathological assessment of those lesions to inform adjuvant management and prognosis. METHODS AND RESULTS A single large-institution cohort of 132 patients who received NAET over a 13-year period was identified. Comprehensive clinical, histopathological and follow-up data were collected. A detailed histological review of a subset with residual post-treatment carcinoma was undertaken. Two carcinomas (both of the lobular type) achieved complete pathological response. Central scarring was seen in 49.3% of tumours post-treatment. Significant changes in tumour type (41.6%), tumour grade (downgrading in one-third of tumours), and progesterone receptor (PR) expression (22.3%), with a switch to PR-negative status in 17.6% of cases, were observed. The last of these was associated with an absence of tumour-infiltrating lymphocytes (P = 0.005). Ten per cent of cases showed a change in HER2 expression (P = 0.002). The median patient survival was 60 months, and downgrading of tumours was associated with better overall survival (P = 0.05). CONCLUSIONS We propose a histological method for assessment of residual carcinoma following NAET, and recommend repeat ER/PR/HER2 testing to inform management and prognosis.
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Affiliation(s)
- Nahla M Badr
- Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, UK.,Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
| | - David Spooner
- Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jane Steven
- Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Andrea Stevens
- Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Abeer M Shaaban
- Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, UK.,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, Khan SA, Loibl S, Morris EA, Perez A, Regan MM, Spears PA, Sudheendra PK, Symmans WF, Yung RL, Harvey BE, Hershman DL. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. J Clin Oncol 2021; 39:1485-1505. [PMID: 33507815 PMCID: PMC8274745 DOI: 10.1200/jco.20.03399] [Citation(s) in RCA: 541] [Impact Index Per Article: 135.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/04/2020] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer. METHODS ASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options. RESULTS A total of 41 articles met eligibility criteria and form the evidentiary basis for the guideline recommendations. RECOMMENDATIONS Patients undergoing neoadjuvant therapy should be managed by a multidisciplinary care team. Appropriate candidates for neoadjuvant therapy include patients with inflammatory breast cancer and those in whom residual disease may prompt a change in therapy. Neoadjuvant therapy can also be used to reduce the extent of local therapy or reduce delays in initiating therapy. Although tumor histology, grade, stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) expression should routinely be used to guide clinical decisions, there is insufficient evidence to support the use of other markers or genomic profiles. Patients with triple-negative breast cancer (TNBC) who have clinically node-positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; those with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy. Carboplatin may be offered to patients with TNBC to increase pathologic complete response. There is currently insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy. In patients with hormone receptor (HR)-positive (HR-positive), HER2-negative tumors, neoadjuvant chemotherapy can be used when a treatment decision can be made without surgical information. Among postmenopausal patients with HR-positive, HER2-negative disease, hormone therapy can be used to downstage disease. Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy in combination with anti-HER2-positive therapy. Patients with T1aN0 and T1bN0, HER2-positive disease should not be routinely offered neoadjuvant therapy.Additional information is available at www.asco.org/breast-cancer-guidelines.
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Affiliation(s)
- Larissa A Korde
- Clinical Investigations Branch, CTEP, DCTD, National Cancer Institute, Bethesda, MD
| | | | - Lisa A Carey
- University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC
| | | | | | | | | | | | | | - Alejandra Perez
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Plantation, FL
| | | | - Patricia A Spears
- University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC
| | | | | | | | | | - Dawn L Hershman
- Herbert Irving Comprehensive Cancer Center at Columbia University, New York, NY
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Comprehensive analysis of expression and prognostic value of the claudin family in human breast cancer. Aging (Albany NY) 2021; 13:8777-8796. [PMID: 33714203 PMCID: PMC8034964 DOI: 10.18632/aging.202687] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 01/25/2021] [Indexed: 12/21/2022]
Abstract
Claudins (CLDN) are structural components of tight junctions that function in paracellular transport and maintain the epithelial barrier function. Altered expression and distribution of members of the claudin family have been implicated in several cancers including breast cancer (BC). We performed a comprehensive analysis of the expression and prognostic value of claudins in BC using various online databases. Compared with normal tissues, CLDN3, 4, 6, 7, 9, and 14 were upregulated in BC tissues, whereas CLDN2, 5, 8, 10, 11, 15, 19, and 20 were downregulated. A high expression of CLDN2, 5, 6, 9, 10, 11, and 14–20 was associated with better relapse-free survival (RFS), whereas a high CLDN3 expression correlated with poor RFS. In addition, a high expression of CLDN3, 4, 14, and 20 was associated with poor overall survival (OS), whereas that of CLDN5 and CLDN11 was linked to a better OS. Although METABRIC and TCGA datasets revealed 22% and 27% gene alterations, respectively, in the members of the claudin family, these were not associated with survival. These findings suggest CLDN3, 5, and 11 could be promising therapeutic targets for patients with BC.
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Iwamoto M, Takei H, Ninomiya J, Asakawa H, Kurita T, Yanagihara K, Iida S, Sakatani T, Ohashi R. Neoadjuvant endocrine therapy in women with operable breast cancer: A retrospective analysis of real-world use. J NIPPON MED SCH 2021; 88:448-460. [PMID: 33692294 DOI: 10.1272/jnms.jnms.2021_88-603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing its role in breast cancer care. MATERIALS AND METHODS In a consecutive series of women with operable breast cancer who received NET for ≥28 days, NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survivals, were examined for the correlation with clinicopathological factors. RESULTS NET objectives were for surgery extent reduction in 49 patients, surgery avoidance in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1923), 869.8 (range, 36-4859), and 55.8 (range, 39-113) days in the above cohorts (success: 79.6%, 64.5%, and 100%), respectively, with significant difference. In patients of the former two cohorts, better progression-free survival was significantly correlated with stage 0 or I, ductal carcinoma in situ or invasive ductal carcinoma, ≥71% estrogen receptor (ER) positivity, and the surgery extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly correlated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high Preoperative Endocrine Prognostic Index, at surgery after NET. Better recurrence-free survival after surgery was significantly correlated with high ER expression after NET and high PgR expression before and after NET. CONCLUSIONS NET can help to reduce the surgery extent or to avoid surgery in women with breast cancer of early-stage, ductal carcinoma, or high ER expression. NET may also contribute to appropriate decision of postoperative systemic therapy to improve survivals.
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Affiliation(s)
- Miki Iwamoto
- Department of Breast Surgery and Oncology, Nippon Medical School.,Department of Breast Surgery, Gyotoku General Hospital
| | - Hiroyuki Takei
- Department of Breast Surgery and Oncology, Nippon Medical School
| | - Jun Ninomiya
- Department of Breast Surgery and Oncology, Nippon Medical School.,Ninomiya Hospital
| | - Hideki Asakawa
- Department of Breast Surgery and Oncology, Nippon Medical School.,Department of Breast Surgery and Oncology, Tokyo Kyosai Hospital
| | - Tomoko Kurita
- Department of Breast Surgery and Oncology, Nippon Medical School
| | - Keiko Yanagihara
- Department of Breast Surgery and Oncology, Nippon Medical School.,Department of Breast Surgery and Oncology, Tamanagayama Hospital
| | - Shinya Iida
- Department of Breast Surgery and Oncology, Nippon Medical School.,Department of Breast Surgery and Oncology, Nippon Medical School Chibahokusoh Hospital
| | - Takashi Sakatani
- Department of Integrated Diagnostic Pathology, Nippon Medical School
| | - Ryuji Ohashi
- Department of Integrated Diagnostic Pathology, Nippon Medical School
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Zhang J, Lu CY, Chen HM, Wu SY. Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity. JAMA Netw Open 2021; 4:e211785. [PMID: 33710293 PMCID: PMC7955271 DOI: 10.1001/jamanetworkopen.2021.1785] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
IMPORTANCE Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer. OBJECTIVE To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT. DESIGN, SETTING, AND PARTICIPANTS This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020. EXPOSURES NET vs NACT for IDC with strong HR positivity and ERBB2 negativity. MAIN OUTCOMES AND MEASURES The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments. RESULTS A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P < .001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P = .009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P = .005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P < .001). CONCLUSIONS AND RELEVANCE The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.
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Affiliation(s)
- Jiaqiang Zhang
- Department of Anesthesiology and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Chang-Yun Lu
- Department of General Surgery, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
| | - Ho-Min Chen
- Department of Food Nutrition and Health Biotechnology, Asia University College of Medical and Health Science, Taichung, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
| | - Szu-Yuan Wu
- Department of Anesthesiology and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Department of Food Nutrition and Health Biotechnology, Asia University College of Medical and Health Science, Taichung, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
- Department of Healthcare Administration, Asia University College of Medical and Health Science, Taichung, Taiwan
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
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Obeng-Gyasi S, Coles CE, Jones J, Sacks R, Lightowlers S, Bliss JM, Brunt AM, Haviland JS, Kirby AM, Kalinsky K. When the World Throws You a Curve Ball: Lessons Learned in Breast Cancer Management. Am Soc Clin Oncol Educ Book 2021; 41:1-11. [PMID: 33956493 DOI: 10.1200/edbk_320691] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
In the care of patients with operable breast cancer, there has been a shift toward increasing use of neoadjuvant therapy. There are benefits to neoadjuvant therapy, such as monitoring for response, as well as an increased rate of breast conservation and reduction of potential morbidity associated with breast surgery, including axillary management. Among patients with highly proliferative tumors, such as HER2-positive or triple-negative breast cancer, those with residual disease are at higher risk of recurrence, which informs the recommended systemic therapy in the adjuvant setting. For instance, in patients with residual disease after neoadjuvant chemotherapy and HER2-targeted therapy, there is a role for adjuvant trastuzumab emtansine for those with residual disease at the time of surgery. The same holds true regarding the role of adjuvant capecitabine in patients with residual disease after neoadjuvant chemotherapy. With the added complexities of treating patients in the era of the COVID-19 outbreak, additional considerations are critical, including initiation of surgery within an appropriate time from completion of neoadjuvant therapy. National consensus guidelines on time to surgery must be developed to improve measurement and comparison across systems. In addition, there is emerging radiation treatment management research addressing a number of factors, including hypofractionation, role of proton beam therapy, safe omission of radiotherapy, and preoperative radiotherapy with or without drug combination. In this article, the multidisciplinary approach of treating patients with operable breast cancer is highlighted, with updates and future considerations described.
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Affiliation(s)
- Samilia Obeng-Gyasi
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH
| | - Charlotte E Coles
- Department of Oncology, University of Cambridge, Cambridge, United Kingdom
| | - Jade Jones
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Ruth Sacks
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Sara Lightowlers
- Department of Oncology, University of Cambridge, Cambridge, United Kingdom
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, United Kingdom
| | - Judith M Bliss
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, United Kingdom
| | - A Murray Brunt
- School of Medicine, University of Keele, Keele, United Kingdom
| | - Joanne S Haviland
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, United Kingdom
| | - Anna M Kirby
- Department of Radiotherapy, Royal Marsden National Health Service Foundation Trust and The Institute of Cancer Research, London, United Kingdom
| | - Kevin Kalinsky
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
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Lerebours F, Cabel L, Pierga JY. Neoadjuvant Endocrine Therapy in Breast Cancer Management: State of the Art. Cancers (Basel) 2021; 13:902. [PMID: 33670042 PMCID: PMC7926493 DOI: 10.3390/cancers13040902] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/09/2021] [Accepted: 02/15/2021] [Indexed: 11/23/2022] Open
Abstract
Endocrine therapy is the mainstay of treatment in HR+/HER2- breast cancers, which represent about 70% of all breast cancers. Neoadjuvant therapy has been developed since the 1990s to address several issues, including breast-conserving surgery (BCS) and improvement of survival rates. For a long time, neoadjuvant endocrine therapy (NET) was confined to frail patients in order to improve surgery outcome. Since the 2000s, NET now plays a central role as a research tool for predictive endocrine sensitivity biomarkers and targeted therapies. One of the major issues in early HR+/HER2- breast cancer is to identify patients in whom chemotherapy can be safely withheld. In vivo assessment of response to NET might be the best treatment strategy to address this issue.
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Affiliation(s)
- Florence Lerebours
- Medical Oncology Department, Institut Curie, 92210 Saint-Cloud, France; (L.C.); (J.-Y.P.)
| | - Luc Cabel
- Medical Oncology Department, Institut Curie, 92210 Saint-Cloud, France; (L.C.); (J.-Y.P.)
| | - Jean-Yves Pierga
- Medical Oncology Department, Institut Curie, 92210 Saint-Cloud, France; (L.C.); (J.-Y.P.)
- Department of Medicine, University of Paris, 75006 Paris, France
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Kawate T, Yoshida A, Sugae S, Asaga S, Kaise H, Saji S, Yamauchi C, Miyoshi Y, Yamauchi H, Ishikawa T. Recommendations for the management of breast cancer patients during the COVID-19 pandemic from the Japan Breast Cancer Society. Breast Cancer 2021; 28:247-253. [PMID: 33609229 PMCID: PMC7895736 DOI: 10.1007/s12282-020-01214-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 12/24/2020] [Indexed: 11/30/2022]
Abstract
The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 remains a major global crisis and continues to spread relentlessly around the world. In Japan, the number of infected people has incrementally increased since April 2020. The COVID-19 pandemic has exerted a major impact not only on our daily lives but also on healthcare. As the infection continues to spread, many medical institutions have devoted all efforts to minimize the risk of infection not only for patients but also for medical personnel by prioritizing medical care, reserving treatment, and extending consultation intervals. Cancer treatment is one of the priorities for medical care even during an epidemic infection as there is a concern of decreasing curability or therapeutic effect from postponement. As the COVID-19 situation evolves rapidly, we created an informative triage to provide appropriate medical treatment to breast cancer patients. In this triage, we offer guidance on preparing for the impact of the COVID-19 pandemic in breast cancer patients, prioritizing triage and diagnostic procedures, and providing advice on surgical, radiation, and oncological treatments.
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Affiliation(s)
- Takahiko Kawate
- Department of Breast Oncology and Surgery, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku, Tokyo, 160-0023, Japan
| | - Atsushi Yoshida
- Department of Breast Surgical Oncology, St. Luke's International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan
| | - Sadatoshi Sugae
- Department of Breast Surgery, Fujisawa City Hospital, 2-6-1, Fujisawa, Fujisawa, Kanagawa, 251-8550, Japan
| | - Souta Asaga
- Department of Breast Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka, Tokyo, 181-8611, Japan
| | - Hiroshi Kaise
- Department of Breast Oncology and Surgery, Tokyo Medical University Ibaraki Medical Center, 3-20-1, Amimachi-Chuo, Inashiki, Ibaraki, 300-0395, Japan
| | - Shigehira Saji
- Department of Medical Oncology, Fukushima Medical University, 1, Hikarigaoka, Fukushima, Fukushima, 950-1295, Japan
| | - Chikako Yamauchi
- Department of Radiotherapy, Shiga General Hospital, 5-4-30, Moriyama, Moriyama, Shiga, 524-8524, Japan
| | - Yasuo Miyoshi
- Department of Breast and Endocrine Surgery, Hyogo College of Medicine Hospital, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hideko Yamauchi
- Department of Breast Surgical Oncology, St. Luke's International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan
| | - Takashi Ishikawa
- Department of Breast Oncology and Surgery, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku, Tokyo, 160-0023, Japan.
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da Silva LR, de Andrade CA, Brenelli F, Ramalho S, Reinert T, de Souza ABA, da Silva AER, de Paula Leite Kraft MB, de Vasconcelos VCA, Frasson AL, Torresan RZ, Cabello C, Ellis MJ, Zeferino LC. Real-world data on neoadjuvant endocrine therapy in ER-positive/HER2-negative breast cancer. Breast Cancer Res Treat 2021; 186:753-760. [PMID: 33543355 DOI: 10.1007/s10549-020-06076-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 12/23/2020] [Indexed: 11/27/2022]
Abstract
PURPOSE Neoadjuvant endocrine therapy (NET) has been shown to be effective in ER-positive/HER2-negative breast cancer in clinical trials. However, adoption in clinical practice is still limited. Real-world data may provide useful insights into effectiveness, toxicities and quality of care, potentially rendering clinical trial results to the real-world setting. Our purpose was to report real-world data of a cohort of postmenopausal patients submitted to NET. METHODS This prospective cohort study evaluated 146 postmenopausal female patients with ER-positive/HER2-negative breast cancer treated with NET at three tertiary hospitals between 2016 and 2018. Clinicopathological information were collected prospectively. Preoperative Endocrine Prognostic Index (PEPI) score was calculated for tumors submitted to at least 16 weeks of NET. RESULTS Median age was 67 years old, and 87.8% had stage I-II disease. Most tumors had histological grade II (76.1%). Median pretreatment Ki67 expression was 10%. Aromatase inhibitor was used in 99.5% of patients, and median treatment duration was 21.0 weeks. No tumor progressed during NET. Breast-conserving surgery was performed in the majority of patients (63.0%), as well as sentinel lymph-node biopsy (76.7%). Pathological complete response rate was 1.0%. 43 patients (29.5%) had PEPI score 0, and 26% had PEPI scores 4-5. Posttreatment Ki67 median expression was 3.0%, and only five tumors (3.4%) showed marked increase in Ki67 expression during treatment. Seven patients (4.8%) had HER2-positive residual disease, and were treated with adjuvant chemotherapy plus trastuzumab. CONCLUSIONS Our real-world data shows that NET is effective and safe in postmenopausal patients with ER-positive/HER2-negative breast cancer. Postmenopausal status and low-risk luminal tumor features (luminal A-like) should be used as selection criteria to ensure the best results with NET.
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Affiliation(s)
- Leonardo Roberto da Silva
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Camila Annicchino de Andrade
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Fabrício Brenelli
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Susana Ramalho
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Tomás Reinert
- Centro de Pesquisa da Serra Gaúcha (CEPESG), Caxias do Sul, Brazil.,Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
| | | | - Ana Elisa Ribeiro da Silva
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Maria Beatriz de Paula Leite Kraft
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Vivian Castro Antunes de Vasconcelos
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Antônio Luiz Frasson
- Breast Cancer Center, Hospital São Lucas, Pontifical Catholic University of Rio Grande Do Sul (PUCRS), Porto Alegre, Brazil
| | - Renato Zochio Torresan
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Cesar Cabello
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil
| | - Matthew J Ellis
- Lester and Sue Smith Breast Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Luiz Carlos Zeferino
- Faculty of Medical Sciences, Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), R Alexander Fleming 101-Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-881, Brazil.
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Schmidt H, Zhaveri S, Valente C, Pisapati K, Pickholz E, Weltz S, Nayak A, Oza T, Corben A, Weltz C, Port E, Jaffer S. Response in breast vs axilla after neoadjuvant treatment and implications for nonoperative management of invasive breast cancer. Breast J 2021; 27:120-125. [PMID: 33393166 DOI: 10.1111/tbj.14125] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 12/31/2022]
Abstract
Improved imaging and neoadjuvant chemotherapy (NAT) have led to higher pathologic complete response rates (pCR) in patients with invasive breast cancer. This has questioned the necessity of surgery and axillary lymph node (ALN) dissection in these patients. Prospective clinical trials are implementing extensive core biopsies of the tumor bed of patients with clinical complete response as a means to identify and spare them breast surgery. In addition, it is anticipated that patients with pCR are most likely going to have no or minimal disease in ALN as well. To verify the feasibility of these trials, we performed a pathologic analysis of all our patients who have undergone NAT from 2009 to present. Using pathology data base, we identified 362 patients treated with neoadjuvant chemotherapy followed by surgery. Clinical and pathologic information including gross and microscopic descriptions as well as biomarker status was collected. pCR was 50% for patients with negative ALN pretreatment but only 28% for patients with positive ALN at diagnosis. Despite achieving pCR in the breast, up to 10% of patients with positive ALN and 1% with negative ALN had persistent disease. Eight percent of patients that were presumed to have no ALN disease either clinically and or by imaging were found to have metastatic carcinoma in ALN. The metastases were predominantly (80%) <5 mm, and not palpable on physical examination and or due to biopsy sampling error. pCR in breast and ALN directly correlated with tumor size, ALN disease, and Her2 positive and triple negative receptor phenotype. In breast cancer patients who are node positive at time of diagnosis with pCR in the breast after neoadjuvant chemotherapy, residual lymph node disease was very uncommon. Further study is warranted to select patients who may avoid breast and axillary surgery post neoadjuvant chemotherapy.
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Affiliation(s)
- Hank Schmidt
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shruti Zhaveri
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Christopher Valente
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kereeti Pisapati
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Eliana Pickholz
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sarah Weltz
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Anupma Nayak
- Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Twisha Oza
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Adriana Corben
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Christina Weltz
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Elisa Port
- Breast Surgical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shabnam Jaffer
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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