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Nyqvist-Streng J, Helou M, Helou K, Chamalidou C, Kovács A, Parris TZ. The prognostic value of changes in Ki67 following neoadjuvant chemotherapy in residual triple-negative breast cancer: a Swedish nationwide registry-based study. Breast Cancer Res Treat 2025; 210:719-736. [PMID: 39799529 PMCID: PMC11953087 DOI: 10.1007/s10549-025-07610-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 01/03/2025] [Indexed: 01/15/2025]
Abstract
PURPOSE To evaluate the prognostic significance of changes in pre- and post-neoadjuvant chemotherapy (NACT) Ki67 in patients with primary invasive triple-negative breast cancer (TNBC). METHODS Population-based registry data were retrieved for patients diagnosed with TNBC between 2007 and 2021 (n = 9262). Multivariable Cox regression analysis was performed for disease-specific survival (DSS) and overall survival (OS) adjusted for age and residual disease in the breast and nodes (RDBN). RESULTS Of the 1777 TNBC patients receiving NACT, 54 achieved pathologic complete response (pCR) and 755 had residual disease. Most patients were overweight with stage II disease (78%), grade 3 tumors (53%), and RDBN score 3 (42%). Compared to baseline, tumor size (30 vs. 15 mm; P < 0.0001) and Ki67 levels (63% vs. 48%; P < 2.2e - 16) generally decreased after NACT. Although only 5% of samples increased in size, Ki67 levels often remained unchanged (75%) or increased (0.9%) after treatment, respectively. However, 34% of patients discontinued treatment. Patients showing no changes in Ki67% had more unfavorable OS (P < 0.0001) and DSS (P = 0.00032), with significantly lower 5-year survival probabilities (OS: 66%; DSS: 78%) than those with decreased Ki67% (OS: 87%; DSS: 89%). All patients reaching pCR were alive 5 years after diagnosis. However, only the RDBN score was an independent predictor of survival in the multivariable analyses. CONCLUSION Ki67 often remained unchanged in TNBC patients treated with neoadjuvant chemotherapy, resulting in adverse clinical outcomes. These findings highlight the need for individualized treatment regimens and dynamic monitoring of TNBC patients with high Ki67 post-NACT.
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Affiliation(s)
- Jenny Nyqvist-Streng
- Department of Surgery, Region Västra Götaland, Skaraborg Hospital, Skövde, Sweden.
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
| | - Mikael Helou
- Department of Psychiatry, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Khalil Helou
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Chaido Chamalidou
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Oncology, Region Västra Götaland, Skaraborg Hospital, Skövde, Sweden
| | - Anikó Kovács
- Department of Clinical Pathology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Toshima Z Parris
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Kim H, Kang J, Park H, Chun Y, Kim Y. Comparing the Combination of Clinical Risk and Ki-67 Using EndoPredict as an Alternative to Multigene Assays in Prognostic Evaluation of Breast Cancer. Clin Breast Cancer 2025:S1526-8209(25)00045-X. [PMID: 40155251 DOI: 10.1016/j.clbc.2025.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 02/10/2025] [Accepted: 02/28/2025] [Indexed: 04/01/2025]
Abstract
PURPOSE Many studies have examined the relationship between prognostic factors and multigene assays; however, their use as alternatives remains insufficient. This study evaluated the concordance of the combination of clinical risk (CR)-which was determined using the modified version of Adjuvant! Online-and the Ki-67 index using EndoPredict (EP). METHODS Retrospective data from 709 patients were analyzed. The diagnostic accuracy, including concordance, was assessed between CR and EP (EPclin risk vs. EP risk), along with the Ki-67 index (cut-off: 20%). The clinical significance was analyzed using an area under the receiver operating characteristic (ROC) curve. RESULTS EPclin risk showed higher concordance with both CR and Ki-67 than EP risk, and CR showed higher concordance with both EPclin and EP risk than Ki-67. Differences in concordance with CR based on Ki-67 were limited; however, the negative predictive value (NPV) increased in the Ki-67 < 20% group (86.9% in EPclin), whereas the positive predictive value (PPV) increased in the Ki-67 ≥ 20% group (82.7% in EPclin). Improvement in PPV and NPV, as well as concordance, was observed with EPclin in 447 patients with high CR/high Ki-67 and low CR/low Ki-67. ROC analysis confirmed the clinical significance of combining CR with the Ki-67 index, as their combined area under the curve increased to 0.794, compared to 0.660 for CR and 0.742 for Ki-67 alone in EPclin risk. CONCLUSION Integrating CR with the Ki-67 index improves prognostic accuracy and provides a cost-effective alternative to the EP test for luminal-type early breast cancer.
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Affiliation(s)
- Hyunjik Kim
- Department of General Surgery, Breast Cancer Center, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
| | - Jisu Kang
- Department of General Surgery, Breast Cancer Center, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
| | - Heungkyu Park
- Department of General Surgery, Breast Cancer Center, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
| | - Yongsoon Chun
- Department of General Surgery, Breast Cancer Center, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
| | - Yunyeong Kim
- Department of General Surgery, Breast Cancer Center, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea.
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Pan X, Wei C, Su J, Fang M, Lin Q, Qin Y, Gao J, Zhao J, Zhao H, Liu F. A comprehensive analysis of the prognostic value, expression characteristics and immune correlation of MKI67 in cancers. Front Immunol 2025; 16:1531708. [PMID: 40070823 PMCID: PMC11894575 DOI: 10.3389/fimmu.2025.1531708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
Background nuclear-associated antigen Ki67 (Ki67) emerges as a clinically practical biomarker for proliferation assessment among many cancer types. However, the definite prognostic value of Ki67 against a specific cancer type has remained vague. This study aims to perform a comprehensive pan-cancer analysis of the prognosis value of Ki67 across various cancer types. Methods This study explored the expression, prognostic value, and tumor-infiltrating immune of MKI67 in the TCGA database by pan-cancer, and then performed immunohistochemical, correlation analysis and prognostic analysis using 10028 patients of the top 10 cancer patients in China we collected. The correlation between MKI67 expression and survival outcome, clinical features, MSI, TMB, and tumor-infiltrating immune cells by TCGA database, xCell, and TIMER algorithms. Results MKI67 expression was significantly upregulated across varied cancer types verified by datasets. We found MKI67 expression was significantly associated with poor prognosis in LUADLUSC, LIHC, and BRCA patients, but good prognosis in COADREAD and READ patients via Kaplan-Meier survival analysis using 10028 patients collected. These results of our validation were generally consistent with TCGA database except BRCA, COADREAD and READ. Meanwhile, upregulation of MKI67 elevates the degree of immune infiltration of several immune cell subtypes, such as functional T cells, CD4+ T cells, and CD8+ T cells, as well as, MKI67 was related to Cell cycle, Oocyte meiosis, p53 and other pathways. Conclusion Our comprehensive analysis may supply useful guidance on MKI67 applicability across various cancer types. These observed results contribute to the promise of MKI67 in a realistic clinical setting and improve the outcomes of cancer patients.
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Affiliation(s)
- Xiaolan Pan
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Caibiao Wei
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jingyu Su
- Genetic Metabolism Center laboratory, Guangxi Zhuang Autonomous Region Maternal and Child Health Care Hospital, Nanning, China
| | - Min Fang
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Qiumei Lin
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yuling Qin
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jie Gao
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jie Zhao
- Department of Medical Records, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Huiliu Zhao
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Fengfei Liu
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
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Hu J, Dong J, Yang X, Ye Z, Hu G. Erythrocyte modified controlling nutritional status as a biomarker for predicting poor prognosis in post-surgery breast cancer patients. Sci Rep 2025; 15:2071. [PMID: 39814814 PMCID: PMC11736028 DOI: 10.1038/s41598-024-83729-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 12/17/2024] [Indexed: 01/18/2025] Open
Abstract
Nutrition and inflammation are closely related to prognosis in breast cancer patients. However, current nutritional and inflammatory measures predict disease free survival (DFS) of breast cancer are still different, and the most predictive measures remain unknown. This study aimed to compare the predictive effects of commonly used nutritional and inflammatory measures on DFS and to improve existing nutritional or inflammatory measures in order to develop a new model that is more effective for predicting postoperative recurrence and metastasis in breast cancer patients. The clinical data of 536 female breast cancer patients with invasive ductal carcinoma who underwent surgery at Shaoxing People's Hospital from January 2012 to December 2018 were retrospectively evaluated. The predictive effects of nutritional and inflammatory indicators on DFS were evaluated. Machine learning was used to evaluate and rank laboratory indicators, select relatively important variables to modify nutritional or inflammatory indicators with the best predictive power, and evaluate their predictive role in patients' postoperative recurrence and metastasis. Among various metrics predicting DFS, the CONUT score emerged paramount with an area under the curve (AUC) of 0.667. Interestingly, the combination of the erythrocyte levels with the CONUT score (ECONUT) achieved the highest AUC (0.722). The Kaplan-Meier survival analysis showed that the group exhibiting high ECONUT scores experiencing a notably poorer DFS. ECONUT was identified as an independent risk factor for postoperative DFS (P < 0.001). The ECONUT model could provide an effective assessment tool for predicting DFS in breast cancer patients.
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Affiliation(s)
- Jingjing Hu
- School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, China
- Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Zhejiang, 312000, China
| | - Jiaming Dong
- School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, China
| | - Xiang Yang
- School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, China
| | - Zhiyi Ye
- Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Zhejiang, 312000, China
| | - Guoming Hu
- School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
- Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Zhejiang, 312000, China.
- Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou, Zhejiang, China.
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Zwager MC, Yu S, Buikema HJ, de Bock GH, Ramsing TW, Thagaard J, Koopman T, van der Vegt B. Advancing Ki67 hotspot detection in breast cancer: a comparative analysis of automated digital image analysis algorithms. Histopathology 2025; 86:204-213. [PMID: 39104219 PMCID: PMC11649514 DOI: 10.1111/his.15294] [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: 02/27/2024] [Revised: 06/25/2024] [Accepted: 07/20/2024] [Indexed: 08/07/2024]
Abstract
AIM Manual detection and scoring of Ki67 hotspots is difficult and prone to variability, limiting its clinical utility. Automated hotspot detection and scoring by digital image analysis (DIA) could improve the assessment of the Ki67 hotspot proliferation index (PI). This study compared the clinical performance of Ki67 hotspot detection and scoring DIA algorithms based on virtual dual staining (VDS) and deep learning (DL) with manual Ki67 hotspot PI assessment. METHODS Tissue sections of 135 consecutive invasive breast carcinomas were immunohistochemically stained for Ki67. Two DIA algorithms, based on VDS and DL, automatically determined the Ki67 hotspot PI. For manual assessment; two independent observers detected hotspots and calculated scores using a validated scoring protocol. RESULTS Automated hotspot detection and assessment by VDS and DL could be performed in 73% and 100% of the cases, respectively. Automated hotspot detection by VDS and DL led to higher Ki67 hotspot PIs (mean 39.6% and 38.3%, respectively) compared to manual consensus Ki67 PIs (mean 28.8%). Comparing manual consensus Ki67 PIs with VDS Ki67 PIs revealed substantial correlation (r = 0.90), while manual consensus versus DL Ki67 PIs demonstrated high correlation (r = 0.95). CONCLUSION Automated Ki67 hotspot detection and analysis correlated strongly with manual Ki67 assessment and provided higher PIs compared to manual assessment. The DL-based algorithm outperformed the VDS-based algorithm in clinical applicability, because it did not depend on virtual alignment of slides and correlated stronger with manual scores. Use of a DL-based algorithm may allow clearer Ki67 PI cutoff values, thereby improving the clinical usability of Ki67.
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Affiliation(s)
- Mieke C Zwager
- Department of PathologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Shibo Yu
- Department of PathologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Henk J Buikema
- Department of PathologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Geertruida H de Bock
- Department of EpidemiologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | | | | | - Timco Koopman
- Department of PathologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
- Pathologie FrieslandLeeuwardenThe Netherlands
| | - Bert van der Vegt
- Department of PathologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
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Ekholm A, Wang Y, Vallon-Christersson J, Boissin C, Rantalainen M. Prediction of gene expression-based breast cancer proliferation scores from histopathology whole slide images using deep learning. BMC Cancer 2024; 24:1510. [PMID: 39663527 PMCID: PMC11633006 DOI: 10.1186/s12885-024-13248-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 11/25/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND In breast cancer, several gene expression assays have been developed to provide a more personalised treatment. This study focuses on the prediction of two molecular proliferation signatures: an 11-gene proliferation score and the MKI67 proliferation marker gene. The aim was to assess whether these could be predicted from digital whole slide images (WSIs) using deep learning models. METHODS WSIs and RNA-sequencing data from 819 invasive breast cancer patients were included for training, and models were evaluated on an internal test set of 172 cases as well as on 997 cases from a fully independent external test set. Two deep Convolutional Neural Network (CNN) models were optimised using WSIs and gene expression readouts from RNA-sequencing data of either the proliferation signature or the proliferation marker, and assessed using Spearman correlation (r). Prognostic performance was assessed through Cox proportional hazard modelling, estimating hazard ratios (HR). RESULTS Optimised CNNs successfully predicted the proliferation score and proliferation marker on the unseen internal test set (ρ = 0.691(p < 0.001) with R2 = 0.438, and ρ = 0.564 (p < 0.001) with R2 = 0.251 respectively) and on the external test set (ρ = 0.502 (p < 0.001) with R2 = 0.319, and ρ = 0.403 (p < 0.001) with R2 = 0.222 respectively). Patients with a high proliferation score or marker were significantly associated with a higher risk of recurrence or death in the external test set (HR = 1.65 (95% CI: 1.05-2.61) and HR = 1.84 (95% CI: 1.17-2.89), respectively). CONCLUSIONS The results from this study suggest that gene expression levels of proliferation scores can be predicted directly from breast cancer morphology in WSIs using CNNs and that the predictions provide prognostic information that could be used in research as well as in the clinical setting.
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Affiliation(s)
- Andreas Ekholm
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, 171 77, Sweden
| | - Yinxi Wang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, 171 77, Sweden
| | | | - Constance Boissin
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, 171 77, Sweden
| | - Mattias Rantalainen
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, 171 77, Sweden.
- MedTechLabs, BioClinicum, Karolinska University Hospital, Stockholm, Sweden.
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Jeropoulos RM, Arroyo J, Davenport M. Predicting and optimising outcome for biliary atresia. Semin Pediatr Surg 2024; 33:151479. [PMID: 39884180 DOI: 10.1016/j.sempedsurg.2025.151479] [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: 10/16/2024] [Accepted: 01/07/2025] [Indexed: 02/01/2025]
Abstract
Biliary atresia (BA) remains a disease of significant morbidity and mortality world-wide. Early and accurate diagnosis facilitates early intervention and improves outcomes. The gold standard in diagnosing BA is a liver biopsy followed by cholangiography, usually performed intra-operatively. Serum markers, like the aspartate aminotransferase-to-platelet ratio, matrix metalloproteinase-7 and several inflammatory cytokines have been recently investigated as non-invasive alternatives with varying degrees of success. Newer immunohistochemical analysis of liver biopsies, such as the expression of secretin receptors and Ki-67, from infants with BA have improved our understanding of the disease process and has shed a little light in predicting post-operative outcomes. There is little standardisation in the care of BA post operatively, though administration of steroids, prevention and treatment of cholangitis with antibiotics and anti-viral therapy for CMV+ve infants are becoming universally accepted as treatment. Experimental stem cell treatments show promise although remain in the out-of-reach future for now in routine clinical practice. This chapter aims to comprehensively describe recent knowledge on predicting the clinical outcomes of infants with BA, as well as optimising their care post operatively.
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Affiliation(s)
- Renos M Jeropoulos
- Dept of Paediatric Surgery, Kings College Hospital, London SE59RS, England, United Kingdom
| | - Jorge Arroyo
- Dept of Paediatric Surgery, Kings College Hospital, London SE59RS, England, United Kingdom
| | - Mark Davenport
- Dept of Paediatric Surgery, Kings College Hospital, London SE59RS, England, United Kingdom.
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Li R, Ke H, Liu P, Yang Q, Li Y, Ke L, Wang X, Wu C, Zhang Y. Mechanisms of Yiai Fuzheng formula in the treatment of triple-negative breast cancer based on UPLC-Q-Orbitrap-HRMS, network pharmacology, and experimental validation. Heliyon 2024; 10:e36579. [PMID: 39319146 PMCID: PMC11419912 DOI: 10.1016/j.heliyon.2024.e36579] [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: 06/21/2024] [Revised: 08/17/2024] [Accepted: 08/19/2024] [Indexed: 09/26/2024] Open
Abstract
Ethnopharmacological relevance Yiai Fuzheng formula (YAFZF), as a Traditional Chinese Medicine (TCM) prescription, has been used widely at Zhongnan Hospital of Wuhan University for its therapeutic effects and high safety on triple-negative breast cancer (TNBC). Objective In this study, we employed ultra-high-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS), network pharmacology, and experimental validation to elucidate the underlying action mechanism of YAFZF in the treatment of TNBC. Methods The key active ingredients in YAFZF were analyzed using UPLC-Q-Orbitrap-HRMS, and then the potential components, target genes and signalling pathways of YAFZF were predicted using the network pharmacological method. We then used molecular docking to visualize the combination characteristics between major active components and macromolecules in the crucial pathway. In vitro experiments were conducted to investigate the inhibitory effects of YAFZF treatment on the cell viability, invasion, and migration of 4T1 and MDA-MB-231 cells. The xenograft TNBC models were constructed using female Balb/c mice, and their body weights, tumour volumes, and weights were monitored during YAFZF treatment. Quantitative real-time PCR (qRT-PCR), Hematoxylin-eosin (HE), immunohistochemistry (IHC) staining, Western blot (WB), and terminal deoxynucleotidyl transferase (TdT)-dUTP nick-end labeling (TUNEL) staining were used for further experimental validation. Results Based on UPLC-Q-Orbitrap-HRMS and network pharmacology analysis, 6 major bioactive components and 153 intersecting genes were obtained for YAFZF against TNBC. Functional enrichment analysis identified that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway might be the mechanism of action of YAFZF in the treatment of TNBC. Molecular docking results suggested that the main active compounds in YAFZF had strong binding energies with the proteins in the PI3K/Akt pathway. In vitro experiments showed that YAFZF inhibited the cell viability, invasion, and migration abilities of TNBC cells. Animal experiments confirmed that YAFZF treatment suppressed tumour cell proliferation and increased apoptotic cells. PCR, HE, WB, and IHC results indicated that YAFZF could suppress xenograft tumour metastases by inhibiting the PI3K/AKT/mTOR pathway regulating the epithelial-mesenchymal transition (EMT) process. Conclusion YAFZF therapy showed its potential for reducing proliferation, invasion, and migration abilities, increasing apoptosis of TNBC cells. Furthermore, YAFZF treated TNBC by inhibiting xenograft tumour distant metastases via the regulation of EMT by the PI3K/Akt/mTOR pathway, suggesting that it may be useful as an adjuvant treatment.
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Affiliation(s)
- Ruijie Li
- Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Haoliang Ke
- Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
| | - Pan Liu
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
| | - Qian Yang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
| | - Yuxin Li
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
| | - Longzhu Ke
- Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Xiuping Wang
- Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
| | - Chaoyan Wu
- Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
| | - Yingwen Zhang
- Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China
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Zhang L, Shen M, Zhang D, He X, Du Q, Liu N, Huang X. Radiomics Nomogram Based on Dual-Sequence MRI for Assessing Ki-67 Expression in Breast Cancer. J Magn Reson Imaging 2024; 60:1203-1212. [PMID: 38088478 DOI: 10.1002/jmri.29149] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND Radiomics has been extensively applied in predicting Ki-67 in breast cancer (BC). However, this is often confined to the exploration of a single sequence, without considering the varying sensitivity and specificity among different sequences. PURPOSE To develop a nomogram based on dual-sequence MRI derived radiomic features combined with clinical characteristics for assessing Ki-67 expression in BC. STUDY TYPE Retrospective. POPULATION 227 females (average age, 51 years) with 233 lesions and pathologically confirmed BC, which were divided into the training set (n = 163) and test set (n = 70). FIELD STRENGTH/SEQUENCE 3.0-T, T1-weighted dynamic contrast-enhanced MRI (DCE-MRI) and apparent diffusion coefficient (ADC) maps from diffusion-weighted MRI (EPI sequence). ASSESSMENT The regions of interest were manually delineated on ADC and DCE-MRI sequences. Three radiomics models of ADC, DCE-MRI, and dsMRI (combined ADC and DCE-MRI sequences) were constructed by logistic regression and the radiomics score (Radscore) of the best model was calculated. The correlation between Ki-67 expression and clinical characteristics such as receptor status, axillary lymph node (ALN) metastasis status, ADC value, and time signal intensity curve was analyzed, and the clinical model was established. The Radscore was combined with clinical predictors to construct a nomogram. STATISTICAL TESTS The independent sample t-test, Mann-Whitney U test, Chi-squared test, Interclass correlation coefficients (ICCs), single factor analysis, least absolute shrinkage and selection operator (LASSO), logistic regression, receiver operating characteristics, Delong test, Hosmer_Lemeshow test, calibration curve, decision curve. A P-value <0.05 was considered statistically significant. RESULTS In the test set, the prediction efficiency of the dsMRI model (AUC = 0.862) was higher than ADC model (AUC = 0.797) and DCE-MRI model (AUC = 0.755). With the inclusion of estrogen receptor (ER) and ALN metastasis, the nomogram displayed quality improvement (AUC = 0.876), which was superior to the clinical model (AUC = 0.787) and radiomics model. DATA CONCLUSION The nomogram based on dsMRI radiomic features and clinical characteristics may be able to assess Ki-67 expression in BC. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 3.
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Affiliation(s)
- Li Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Mengyi Shen
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Dingyi Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xin He
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Qinglin Du
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Nian Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xiaohua Huang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Bai L, You C, Zhou J, Xie L, Zhu X, Chang C, Zhi W. Quantitative Analysis of Shear Wave Elastography and US-Guided Diffuse Optical Tomography for Evaluating Biological Characteristics of Breast Cancer. Acad Radiol 2024; 31:3489-3498. [PMID: 38548533 DOI: 10.1016/j.acra.2024.03.006] [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: 01/25/2024] [Revised: 02/19/2024] [Accepted: 03/04/2024] [Indexed: 10/01/2024]
Abstract
RATIONALE AND OBJECTIVES Shear Wave Elastography (SWE) and Ultrasound-guided Diffuse Optical Tomography (US-guided DOT) demonstrate promise in distinguishing between benign and malignant breast lesions. This study aims to assess the feasibility and correlation of SWE and US-guided DOT in evaluating the biological characteristics of breast cancer. MATERIALS AND METHODS A cohort of 235 breast cancer patients with 238 lesions, scheduled for surgery within one to three days, underwent B-mode ultrasound (US), US-guided DOT, and SWE. Parameters such as Total Hemoglobin Concentration (THC), Maximal Elasticity (Emax), Mean Elasticity (Emean), Standard Deviation of Elasticity (Esd), and Area Ratio were measured. Correlation with post-surgical pathology reports was examined to explore associations between THC, SWE Parameters, and pathology characteristics. RESULTS Lesions in patient groups with ER-, PR-, HER2 + , high Ki67, LVI+ , and ALN+ exhibited higher THC, Emax, and Esd compared to groups with ER+ , PR+ , HER2-, low Ki67, LVI-, and ALN-. The increase was seen in all grades of IDC-I to -III. THC significantly correlated with Smax (r = 0.340, P < 0.001), Emax (r = 0.339, P < 0.001), Emean (r = 0.201, P = 0.003), and Esd (r = 0.313, P < 0.001). CONCLUSION US-guided DOT and SWE prove valuable for the quantitative assessment of breast cancer's biological characteristics, with THC positively correlated with Emax, Emean, and Esd.
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Affiliation(s)
- Lu Bai
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No 270, Dong'an Road, Xuhui District, Shanghai 200032, China
| | - Chao You
- Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jin Zhou
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No 270, Dong'an Road, Xuhui District, Shanghai 200032, China
| | - Li Xie
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoli Zhu
- Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Cai Chang
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No 270, Dong'an Road, Xuhui District, Shanghai 200032, China
| | - Wenxiang Zhi
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No 270, Dong'an Road, Xuhui District, Shanghai 200032, China.
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11
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Miligy IM, Badr N, Stevens A, Spooner D, Awasthi R, Mir Y, Khurana A, Sharma V, Chandaran U, Rakha EA, Maurice Y, Kearns D, Oweis R, Asar A, Ironside A, Shaaban AM. Pathological Changes Following Neoadjuvant Endocrine Therapy (NAET): A Multicentre Study of 391 Breast Cancers. Int J Mol Sci 2024; 25:7381. [PMID: 39000487 PMCID: PMC11242101 DOI: 10.3390/ijms25137381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 06/30/2024] [Accepted: 07/02/2024] [Indexed: 07/16/2024] Open
Abstract
Oestrogen receptor (ER)-positive breast cancer (BC) is generally well responsive to endocrine therapy. Neoadjuvant endocrine therapy (NAET) is increasingly being used for downstaging ER-positive tumours. This study aims to analyse the effect of NAET on a well-characterised cohort of ER-positive BC with particular emphasis on receptor expression. This is a retrospective United Kingdom (UK) multicentre study of 391 patients who received NAET between October 2012 and October 2020. Detailed analyses of the paired pre- and post-NAET morphological changes and hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression were performed. The median duration of NAET was 86 days, with median survival and overall survival rates of 380 days and 93.4%, respectively. A total of 90.3% of cases achieved a pathological partial response, with a significantly higher rate of response in the HER2-low cancers. Following NAET, BC displayed some pathological changes involving the tumour stroma including central scarring and an increase in tumour infiltrating lymphocytes (TILs) and tumour cell morphology. Significant changes associated with the duration of NAET were observed in tumour grade (30.6% of cases), with downgrading identified in 19.3% of tumours (p < 0.001). The conversion of ER status from positive to low or negative was insignificant. The conversion of progesterone receptor (PR) and HER2 status to negative status was observed in 31.3% and 38.1% of cases, respectively (p < 0.001). HER2-low breast cancer decreased from 63% to 37% following NAET in the paired samples. Significant morphological and biomarker changes involving PR and HER2 expression occurred following NAET. The findings support biomarker testing on pre-treatment core biopsies and post-treatment residual carcinoma.
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Affiliation(s)
- Islam M. Miligy
- Cellular Pathology, Queen Elizabeth Hospital, Birmingham B15 2GW, UK; (I.M.M.); (R.A.); (D.K.)
- Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom 11352, Egypt;
| | - Nahla Badr
- Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom 11352, Egypt;
| | - Andrea Stevens
- Oncology Department, Queen Elizabeth Hospital, Birmingham B15 2GW, UK; (A.S.); (D.S.)
| | - David Spooner
- Oncology Department, Queen Elizabeth Hospital, Birmingham B15 2GW, UK; (A.S.); (D.S.)
| | - Rachna Awasthi
- Cellular Pathology, Queen Elizabeth Hospital, Birmingham B15 2GW, UK; (I.M.M.); (R.A.); (D.K.)
| | - Yasmeen Mir
- Pathology, Liverpool University Hospitals NHS Foundation Trust, Liverpool L7 8XP, UK; (Y.M.); (A.K.); (V.S.)
| | - Anuj Khurana
- Pathology, Liverpool University Hospitals NHS Foundation Trust, Liverpool L7 8XP, UK; (Y.M.); (A.K.); (V.S.)
| | - Vijay Sharma
- Pathology, Liverpool University Hospitals NHS Foundation Trust, Liverpool L7 8XP, UK; (Y.M.); (A.K.); (V.S.)
| | - Usha Chandaran
- Histopathology Department, Salford Royal Hospital, Salford M6 8HD, UK;
| | - Emad A. Rakha
- Histopathology Department, Nottingham City Hospital, Nottingham NG5 1PB, UK;
| | - Yasmine Maurice
- Histopathology Department, Heartlands General Hospital, Birmingham B9 5SS, UK;
| | - Daniel Kearns
- Cellular Pathology, Queen Elizabeth Hospital, Birmingham B15 2GW, UK; (I.M.M.); (R.A.); (D.K.)
| | - Rami Oweis
- Histopathology Department, Rotherham Foundation Trust, Rotherham S60 2UD, UK; (R.O.); (A.A.)
| | - Amal Asar
- Histopathology Department, Rotherham Foundation Trust, Rotherham S60 2UD, UK; (R.O.); (A.A.)
| | | | - Abeer M. Shaaban
- Cellular Pathology, Queen Elizabeth Hospital, Birmingham B15 2GW, UK; (I.M.M.); (R.A.); (D.K.)
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2SY, UK
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12
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Li F, Zhou X, Hu W, Du Y, Sun J, Wang Y. Prognostic predictive value of Ki-67 in stage I-II triple-negative breast cancer. Future Sci OA 2024; 10:FSO936. [PMID: 38827797 PMCID: PMC11140645 DOI: 10.2144/fsoa-2023-0129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 11/06/2023] [Indexed: 06/05/2024] Open
Abstract
Aim: Our research aimed to determine an optimal cutoff value and investigate the prognostic predictive function of Ki-67. Materials & methods: We retrospectively enrolled 1146 patients diagnosed with stage I-II triple-negative breast cancer. Disease-free and overall survival were analyzed using the Kaplan-Meier method and the Cox regression model. Results: We classified Ki-67 >45% as the high group (n = 716). A Ki-67 level of >45% was associated with poorer disease-free survival (p = 0.039) and overall survival (p = 0.029). Lymph node stage, neoadjuvant chemotherapy, and radiotherapy were independent predictive variables of prognosis. Conclusion: Triple-negative breast cancer may be further subcategorized according to the Ki-67 level. Neoadjuvant chemotherapy and postoperative radiotherapy can improve the prognosis of early triple-negative breast cancer.
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Affiliation(s)
- Fengyan Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Xinhui Zhou
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Wendie Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Yujie Du
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Jiayuan Sun
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Yaxue Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
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13
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Zhou JY, Pan CG, Ye Y, Li ZW, Fu WD, Jiang BH. Development and Validation of a Prognostic Nomogram for HR+ HER- Breast Cancer. Cancer Manag Res 2024; 16:491-505. [PMID: 38800665 PMCID: PMC11127650 DOI: 10.2147/cmar.s459714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/08/2024] [Indexed: 05/29/2024] Open
Abstract
Purpose We aimed to develop a nomogram to predict prognosis of HR+ HER2- breast cancer patients and guide the application of postoperative adjuvant chemotherapy. Methods We identified 310 eligible HR+ HER- breast cancer patients and randomly divided the database into a training group and a validation group. The endpoint was disease free survival (DFS). Concordance index (C-index), area under the curve (AUC) and calibration curves were used to evaluate predictive accuracy and discriminative ability of the nomogram. We also compared the predictive accuracy and discriminative ability of our nomogram with the eighth AJCC staging system using overall data. Results According to the training group, platelet-to-lymphocyte ratio (PLR), tumor size, positive lymph nodes and Ki-67 index were used to construct the nomogram of DFS. The C-index of DFS was 0.708 (95% CI: 0.623-0.793) in the training group and 0.67 (95% CI: 0.544-0.796) in the validation group. The calibration curves revealed great consistencies in both groups. Conclusion We have developed and validated a novel and practical nomogram that can provide individual prediction of DFS for patients with HR+ HER- breast cancer. This nomogram may help clinicians in risk consulting and guiding the application of postoperative adjuvant chemotherapy.
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Affiliation(s)
- Jie-Yu Zhou
- Department of Thyroid and Breast Surgery, The Wenzhou Central Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of China
| | - Cheng-Geng Pan
- Department of Thyroid and Breast Surgery, The Wenzhou Central Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of China
| | - Yang Ye
- Department of Thyroid and Breast Surgery, The Wenzhou Central Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of China
| | - Zhi-Wei Li
- Department of Thyroid and Breast Surgery, The Wenzhou Central Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of China
| | - Wei-Da Fu
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China
| | - Bin-Hao Jiang
- Department of Urinary Surgery, Yueqing People’s Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of China
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14
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Kosem YOT, Uzun H, Velidedeoglu M, Kocael P, Dumur S, Simsek O. Clinical significance of serum synaptophysin-like 1 protein levels in breast cancer. J Med Biochem 2024; 43:273-280. [PMID: 38699696 PMCID: PMC11062335 DOI: 10.5937/jomb0-46198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 10/12/2023] [Indexed: 05/05/2024] Open
Abstract
Background Mammography, used for breast cancer (BC) screening, has limitations such as decreased sensitivity in dense breasts. Currently used tumor markers are insufficient in diagnosing breast cancer. In this study, we aimed to investigate the relationship between serum levels of synaptophysin-like protein 1 (SYPL1) and BC and compare SYPL1 with other blood tumor markers. Methods The study group consisted of 80 female patients with a histopathological diagnosis of invasive BC who received no radiotherapy/chemotherapy. The control group was 72 women with no previous history of breast disease and evaluated as Breast Imaging Reporting and Data Systems (BI-RADS 1-2) on imaging. Serum SYPL1, cancer antigen 15-3 (CA 15-3), and carcinoembryonic antigen (CEA) were measured in both groups.
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Affiliation(s)
- Yagmur Ozge Turac Kosem
- Istanbul University-Cerrahpas, Cerrahpa a Faculty of Medicine, Department of General Surgery, Istanbul, Turkey
| | - Hafize Uzun
- Istanbul Atlas University, Faculty of Medicine, Department of Medical Biochemistry, Istanbul, Turkey
| | - Mehmet Velidedeoglu
- Istanbul University-Cerrahpas, Cerrahpa a Faculty of Medicine, Department of General Surgery, Istanbul, Turkey
| | - Pınar Kocael
- Istanbul University-Cerrahpas, Cerrahpa a Faculty of Medicine, Department of General Surgery, Istanbul, Turkey
| | - Seyma Dumur
- Istanbul Atlas University, Faculty of Medicine, Department of Medical Biochemistry, Istanbul, Turkey
| | - Osman Simsek
- Istanbul University-Cerrahpas, Cerrahpa a Faculty of Medicine, Department of General Surgery, Istanbul, Turkey
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15
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Popa CN, Bîrlă R, Daniela D, Iosif C, Chirita E, Mateș IN. Predictive Factors of Neoadjuvant Chemotherapy Response in Breast Cancer Validated by Three Anatomopathological Scores: Residual Cancer Burden, Chevallier System, and Tumor-Infiltrating Lymphocytes. Cureus 2024; 16:e59391. [PMID: 38817506 PMCID: PMC11139452 DOI: 10.7759/cureus.59391] [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: 04/30/2024] [Indexed: 06/01/2024] Open
Abstract
INTRODUCTION The aim of this retrospective, observational, descriptive study was to identify predictors of response to neoadjuvant therapy in breast cancer patients and to validate them using three anatomopathological scores, such as residual cancer burden (RCB) score, Chevallier system, and tumor-infiltrating lymphocytes (TIL) score. MATERIALS AND METHODS We conducted a study on 88 female patients aged 37 to 78 years with confirmed breast cancer who were indicated for neoadjuvant chemotherapy. We analyzed different individual variables (such as age, menarche, and menopause), clinical/imaging characteristics of the breast tumor and axillary nodes, immunohistochemical biomarkers (such as ER/PR/HER2 and Ki67), and histopathological features (such as subtype and grading) in relation to three anatomopathological scores calculated based on the surgical resection specimen. RESULTS The percentage of patients who could have benefited from conservative surgery increased from 6% at the time of diagnosis to 20% post-primary systemic therapy (PST). Age under 49 (p = 0.01), premenopausal status (p < 0.01), no special type (NST) (p = 0.04), high Ki67 (p < 0.01), triple-negative breast cancer (TNBC) (p = 0.02) are positive predictive factors of neoadjuvant therapy, while lobular/mixt carcinoma-type (p = 0.04), luminal A (p = 0.01), positive lymph node (p < 0.01), and low differentiation grade (p = 0.01) are negative predictive factors for the response to PST. CONCLUSION There is a strong correlation between the RCB score and the Chevallier system for quantifying the response to PST, with most predictive factors being confirmed through appropriate statistical analysis for both. TIL score values correlated with only some of the predictors, most likely due to the importance of calculating this score on both biopsy specimens at diagnosis and resection specimens after chemotherapy.
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Affiliation(s)
- Cristian N Popa
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Department of General Surgery I, "Sf. Maria" Clinical Hospital, Bucharest, ROU
| | - Rodica Bîrlă
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Department of General Surgery I, "Sf. Maria" Clinical Hospital, Bucharest, ROU
| | - Dinu Daniela
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Department of General Surgery I, "Sf. Maria" Clinical Hospital, Bucharest, ROU
| | - Cristina Iosif
- Department of Pathology, "Sf. Maria" Clinical Hospital, Bucharest, ROU
| | - Evelina Chirita
- Department of Oncology, "Sf. Maria" Clinical Hospital, Bucharest, ROU
| | - Ioan Nicolae Mateș
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Department of General Surgery I, "Sf. Maria" Clinical Hospital, Bucharest, ROU
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16
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Yang SH, Tey ML, Zhou S, Nitar P, Mariyah H, Sim Y, Kusumawidjaja G, Chay WY, Yong WF, Wong RX. Correlation of Neutrophil-Lymphocyte and Albumin-Globulin Ratios With Outcomes in Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy or Upfront Surgery. J Breast Cancer 2024; 27:105-120. [PMID: 38529588 PMCID: PMC11065497 DOI: 10.4048/jbc.2023.0242] [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: 10/27/2023] [Revised: 12/27/2023] [Accepted: 01/27/2024] [Indexed: 03/27/2024] Open
Abstract
PURPOSE Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer. METHODS This retrospective study included all patients with stage I-III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore. Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests. RESULTS A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13-3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16-0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17-0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07-2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11-3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36-0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09-2.44; p = 0.018). CONCLUSION NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.
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Affiliation(s)
- Shi Hui Yang
- Department of Breast Surgery, Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
| | - Min Li Tey
- Department of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Siqin Zhou
- Clinical Trial officer, National Cancer Centre Singapore, Singapore, Singapore
| | - Phyu Nitar
- Cancer Informatics, National Cancer Centre Singapore, Singapore, Singapore
| | - Hanis Mariyah
- Cancer Informatics, National Cancer Centre Singapore, Singapore, Singapore
| | - Yirong Sim
- Department of Breast Surgery, Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Grace Kusumawidjaja
- Department of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Wen Yee Chay
- Department of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Wong Fuh Yong
- Department of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Ru Xin Wong
- Department of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
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Zambelli A, Gallerani E, Garrone O, Pedersini R, Rota Caremoli E, Sagrada P, Sala E, Cazzaniga ME. Working tables on Hormone Receptor positive (HR+), Human Epidermal growth factor Receptor 2 negative (HER2-) early stage breast cancer: Defining high risk of recurrence. Crit Rev Oncol Hematol 2023; 191:104104. [PMID: 37659765 DOI: 10.1016/j.critrevonc.2023.104104] [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: 01/13/2023] [Revised: 08/10/2023] [Accepted: 08/15/2023] [Indexed: 09/04/2023] Open
Abstract
Hormone-receptor positive (HR+), Human-Epidermal-growth Factor negative (HER2-) breast cancer, including the Luminal A and the Luminal B subtypes, is the most common in women diagnosed with early-stage BC. Despite the advances in screening, surgery and therapies, recurrence still occurs. Therefore, it is important to identify early those factors that significantly impact the recurrence risk. Based on current evidence and their professional expertise, a Panel of oncologists discussed the definition of high risk of recurrence in early breast cancer. Histological grade, nodal involvement, genomic score, histological grade, tumor size, and Ki-67 proliferation index were rated as the most important factors to define the high risk in patients with early breast cancer. All these factors should be considered comprehensively to tailor the choice of treatment to the peculiar characteristics of each patient.
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Affiliation(s)
- A Zambelli
- Department of Biomedical Sciences, Humanitas University and IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - E Gallerani
- Ospedale di Circolo di Varese, Varese, Italy
| | - O Garrone
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, Milan, Italy
| | | | | | - P Sagrada
- Onco-Hematology Unit, ASST Lodi, Lodi, Italy
| | - E Sala
- Oncology Unit, ASST Monza Ospedale San Gerardo, Monza, Italy
| | - M E Cazzaniga
- School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy; Phase 1 Research Unit, Fondazione IRCCS san Gerardo dei Tintori, Monza, Italy.
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18
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Peng Z, Dong X, He M, Zhao Y, Liu Y, Li M, Li G, Wang X, Li L, Hu Y. Elevated profiles of peripheral Th22, Th17, Th2 cells, and decreased percentage of Th1 cells in breast cancer patients. Thorac Cancer 2023; 14:3282-3294. [PMID: 37732365 PMCID: PMC10665788 DOI: 10.1111/1759-7714.15119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 09/10/2023] [Accepted: 09/11/2023] [Indexed: 09/22/2023] Open
Abstract
BACKGROUND Th22 subset is a particular type of CD4+ T helper cells subset. Our study aimed to explore the expression level of circulating Th22, Th17, Th1, and Th2 cells and the possible mechanism of these cells in breast cancer (BC) with different pathological features. METHODS Our study enrolled 43 newly diagnosed BC patients and 30 healthy controls. Frequencies of peripheral Th22, Th17, Th1, and Th2 cells were tested by flow cytometry. Concentrations of IL-22 cytokine in plasma were examined by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was done to test aromatic hydrocarbon receptor (AHR) and RAR-associated orphan receptor C (RORC) gene expression. RESULTS Frequencies of Th22, Th17, Th2 subsets, and the plasma IL-22 level was obviously higher in the BC patients. A positive correlation between Th22 frequency and IL-22 concentration in plasma was detected in BC patients. Furthermore, the percentage of Th22, Th2 subsets in peripheral blood of HER2 positive BC was higher than that in HER2 negative BC patients. A negative correlation between Th1 subset and Ki-67% as well as a positive correlation between Th2 subset and Ki-67% was found in BC patients. The proportion of Th1 cells in BC patients was significantly lower than that of the control group. Expression of AHR and RORC transcription factors were also observed to be upregulated in the BC patients. Furthermore, Th22 cells were positively correlated with BC tumor stage and clinical outcomes. The BC patients with a higher percentage of Th22, Th17, Th1 cells or a lower percentage of Th1 cells showed a decreased trend of survival rate. CONCLUSION Th22, Th17, Th1, and Th2 subsets may play an essential role in BC patients. Th22, Th17, Th1, and Th2 cells may have potential significance to be used as clinical markers in BC patients with different molecular classification. Th22 cells may have potential value in BC patients' outcomes prediction, providing clinical value.
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Affiliation(s)
- Zhiguo Peng
- Department of Organ Transplantation, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Xinyue Dong
- Department of OncologyQilu Hospital of Shandong University Dezhou HospitalDezhouChina
| | - Miao He
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Yajing Zhao
- Department of Hematology, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Yujia Liu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Mo Li
- Department of OncologyWeifang People's HospitalWeifangChina
| | - Guosheng Li
- Department of Hematology, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Xiuwen Wang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Li Li
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Yu Hu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
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Probert J, Dodwell D, Broggio J, Charman J, Dowsett M, Kerr A, McGale P, Taylor C, Darby SC, Mannu GS. Ki67 and breast cancer mortality in women with invasive breast cancer. JNCI Cancer Spectr 2023; 7:pkad054. [PMID: 37567612 PMCID: PMC10500622 DOI: 10.1093/jncics/pkad054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 07/24/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND The percentage of cells staining positive for Ki67 is sometimes used for decision-making in patients with early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut points and the influence of interlaboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for interlaboratory variability and 8 patient and tumor characteristics. METHODS A multicenter cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until December 31, 2020. RESULTS Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early IBC (Ptrend < .001). This relationship remained strong after adjustment for patient and tumor characteristics (Ptrend < .001). Standardization for interlaboratory variability did little to alter these results. For women with Ki67 scores of 0%-5%, 6%-10%, 11%-19%, and 20%-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (95% confidence interval [CI] = 2.8% to 4.0%), 3.7% (95% CI = 3.0% to 4.4%), 3.4% (95% CI = 2.8% to 4.1%), and 3.4% (95% CI = 2.8% to 4.1%), whereas for women with Ki67 scores of 30%-39% and 40%-100%, these risks were higher, at 5.1% (95% CI = 4.3% to 6.2%) and 7.7% (95% CI = 6.6% to 9.1) (Ptrend < .001). Similar results were obtained when the adjusted analysis was repeated with omission of pathological information about tumor size and nodal involvement, which would not be available preoperatively for patients being considered for neoadjuvant therapy. CONCLUSION Our findings confirm the prognostic value of Ki67 scores of 30% or more in women with ER-positive, HER2-negative early IBC, irrespective of interlaboratory variability. These results also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting.
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Affiliation(s)
- Jake Probert
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - David Dodwell
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - John Broggio
- The National Disease Registration Service, NHS England, Leeds, UK
| | - Jackie Charman
- The National Disease Registration Service, NHS England, Leeds, UK
| | | | - Amanda Kerr
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Paul McGale
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Carolyn Taylor
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Sarah C Darby
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Gurdeep S Mannu
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
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20
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Yuan J, Wen Q, Wang H, Wang J, Liu K, Zhan S, Liu M, Gong Z, Tan W. The use of quantitative T1-mapping to identify cells and collagen fibers in rectal cancer. Front Oncol 2023; 13:1189334. [PMID: 37546428 PMCID: PMC10399696 DOI: 10.3389/fonc.2023.1189334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 06/30/2023] [Indexed: 08/08/2023] Open
Abstract
Aim This study aimed to explore the value of T1 mapping in assessing the grade and stage of rectal adenocarcinoma and its correlation with tumor tissue composition. Methods Informed consent was obtained from all rectal cancer patients after approval by the institutional review board. Twenty-four patients (14 women and 10 men; mean age, 64.46 years; range, 35 - 82 years) were enrolled in this prospective study. MRI examinations were performed using 3.0T MR scanner before surgery. HE, immunohistochemical, and masson trichrome-staining was performed on the surgically resected tumors to assess the degree of differentiation, stage, and invasion. Two radiologists independently analyzed native T1 and postcontrast T1 for each lesion, and calculated the extracellular volume (ECV) was calculated from T1 values. Intraclass correlation coefficient (ICC) and Bland-Altman plots were applied to analyze the interobserver agreement of native T1 values and postcontrast T1 values. Student's t-test and one-way analysis of variance (ANOVA) were used to test the differences between T1 mapping parameters and differentiation types, T and N stages, and venous and neural invasion. Pearson correlation coefficients were used to analyze the correlation of T1 mapping extraction parameters with caudal type homeobox 2 (CDX-2), Ki-67 index, and collagen expression. Results Both the native and postcontrast T1 values had an excellent interobserver agreement (ICC 0.945 and 0.942, respectively). Postcontrast T1 values indicated significant differences in venous invasion (t=2.497, p=0.021) and neural invasion (t=2.254, p=0.034). Pearson's correlation analysis showed a significant positive correlation between native T1 values and Ki-67 (r=-0.407, p=0.049). There was a significant positive correlation between ECV and collagen expression (r=0.811, p=.000) and a significant negative correlation between ECV and CDX-2 (r=-0.465, p=0.022) and Ki-67 (r=-0.549, p=0.005). Conclusion Postcontrast T1 value can be used to assess venous and neural invasion in rectal cancer. ECV measurements based on T1 mapping can be used to identify cells and collagen fibers in rectal cancer.
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Affiliation(s)
- Jie Yuan
- Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qun Wen
- Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hui Wang
- Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiaoyan Wang
- Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Kun Liu
- Department of Pathology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Songhua Zhan
- Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengxiao Liu
- MR Scientific Marketing, Diagnostic Imaging, Siemens Healthineers Ltd, Shanghai, China
| | - Zhigang Gong
- Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - WenLi Tan
- Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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21
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Li Y, Zhang Y, Zhou Z, Shang L, Huang Y, Lu X, Cheng S. Predictive value of controlling nutritional status score in postoperative recurrence and metastasis of breast cancer patients with HER2-low expression. Front Oncol 2023; 13:1116631. [PMID: 37492470 PMCID: PMC10365291 DOI: 10.3389/fonc.2023.1116631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 06/19/2023] [Indexed: 07/27/2023] Open
Abstract
Background To investigate the predictive value of controlling nutritional status (CONUT) score in Postoperative Recurrence and Metastasis of Breast Cancer Patients with HER2-Low Expression. Methods The clinicopathological data of 697 female breast cancer patients who pathology confirmed invasive ductal carcinoma and surgery in Harbin Medical University Tumor Hospital from January 2014 to January 2017 were retrospectively analyzed. The relationship between CONUT score and various clinicopathological factors as well as prognosis was evaluated. Results Based on the cut-off point of ROC curve, compared with the low CONUT score group, the high CONUT score group had worse 5-year RFS. In subgroup analysis, compared with the low CONUT group, the high CONUT group had worse prognosis at different TNM stages. Univariate and multivariate results showed that the low CONUT score group had better overall survival and recurrence-free survival than the high CONUT group. Conclusion CONUT score is an independent predictor of postoperative recurrence and metastasis in HER2-low breast cancer patients. It is may be used as an effective tool to predict the recurrence and metastasis of HER2-low breast cancer.
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Affiliation(s)
- Yue Li
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yue Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Zhaoyue Zhou
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Lingmin Shang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuanxi Huang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiangshi Lu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shaoqiang Cheng
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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22
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Zhu Y, Yi M. Editorial: Update on diagnostic and prognostic biomarkers for women's cancers. Front Med (Lausanne) 2023; 10:1225982. [PMID: 37387786 PMCID: PMC10304298 DOI: 10.3389/fmed.2023.1225982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 06/06/2023] [Indexed: 07/01/2023] Open
Affiliation(s)
- Yunxia Zhu
- Department of Obstetrics and Gynecology, Haiyan People's Hospital, Jiaxing, China
| | - Ming Yi
- The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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23
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Yang J, Guo W, Huang R, Bian J, Zhang S, Wei T, He C, Hu Z, Li J, Zhou C, Lu M. Self-assembled albumin nanoparticles induce pyroptosis for photodynamic/photothermal/immuno synergistic therapies in triple-negative breast cancer. Front Immunol 2023; 14:1173487. [PMID: 37342347 PMCID: PMC10279487 DOI: 10.3389/fimmu.2023.1173487] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 04/12/2023] [Indexed: 06/22/2023] Open
Abstract
Triple-negative breast cancer (TNBC) is characterized by a high degree of malignancy, early metastasis, limited treatment, and poor prognosis. Immunotherapy, as a new and most promising treatment for cancer, has limited efficacy in TNBC because of the immunosuppressive tumor microenvironment (TME). Inducing pyroptosis and activating the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) signaling pathway to upregulate innate immunity have become an emerging strategy for enhancing tumor immunotherapy. In this study, albumin nanospheres were constructed with photosensitizer-IR780 encapsulated in the core and cGAS-STING agonists/H2S producer-ZnS loaded on the shell (named IR780-ZnS@HSA). In vitro, IR780-ZnS@HSA produced photothermal therapy (PTT) and photodynamic therapy (PDT) effects. In addition, it stimulated immunogenic cell death (ICD) and activated pyroptosis in tumor cells via the caspase-3-GSDME signaling pathway. IR780-ZnS@HSA also activated the cGAS-STING signaling pathway. The two pathways synergistically boost immune response. In vivo, IR780-ZnS@HSA + laser significantly inhibited tumor growth in 4T1 tumor-bearing mice and triggered an immune response, improving the efficacy of the anti-APD-L1 antibody (aPD-L1). In conclusion, IR780-ZnS@HSA, as a novel inducer of pyroptosis, can significantly inhibit tumor growth and improve the efficacy of aPD-L1.
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Affiliation(s)
- Jianquan Yang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Wen Guo
- Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Rong Huang
- Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Jiaojiao Bian
- Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Siqi Zhang
- Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Ting Wei
- Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Chuanshi He
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Ziyue Hu
- Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Juan Li
- Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Chunyang Zhou
- Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Man Lu
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Department of Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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24
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Ozturk I, Elbe H, Bicer Y, Karayakali M, Onal MO, Altinoz E. Therapeutic role of melatonin on acrylamide-induced hepatotoxicity in pinealectomized rats: Effects on oxidative stress, NF-κB signaling pathway, and hepatocellular proliferation. Food Chem Toxicol 2023; 174:113658. [PMID: 36780936 DOI: 10.1016/j.fct.2023.113658] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/13/2023]
Abstract
Acrylamide (AA) is formed in some foods by the cooking process at high temperatures, and it could be a carcinogen in humans and rodents. The purpose of the current study was to reveal the possible protective effects of melatonin against AA-induced hepatic oxidative stress, hepatic inflammation, and hepatocellular proliferation in pinealectomized rats. Hence, the sham and pinealectomized rats were consecutively given AA alone (25 mg/kg) or with melatonin (10 mg/kg) for 21 days. Melatonin acts as an antioxidant, anti-inflammatory, and antiapoptotic agent and introduces as a therapeutic strategy for AA-induced hepatotoxicity. Melatonin supplementation reduced AA-caused liver damage by decreasing the serum AST, ALT, and ALP levels. Melatonin raised the activities of SOD and CAT and levels of GSH and suppressed hepatic inflammation (TNF-α) and hepatic oxidative stress in liver tissues. Moreover, histopathological alterations and the disturbances in immunohistochemical expression of NF-κB and Ki67 were improved after melatonin treatment in AA-induced hepatotoxicity. Overall, our results demonstrate that melatonin supplementation exhibits adequate hepatoprotective effects against hepatotoxicity of AA on pinealectomized rat liver architecture and the tissue function through the equilibration of oxidant/antioxidant status, the regulation of cell proliferation and the suppression of the release of proinflammatory cytokines.
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Affiliation(s)
- Ipek Ozturk
- Department of Medical Biochemistry, Faculty of Medicine, Karabuk University, Karabuk, Turkey
| | - Hulya Elbe
- Department of Histology and Embryology, Faculty of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey
| | - Yasemin Bicer
- Department of Medical Biochemistry, Faculty of Medicine, Karabuk University, Karabuk, Turkey
| | - Melike Karayakali
- Department of Medical Biochemistry, Faculty of Medicine, Karabuk University, Karabuk, Turkey
| | - Melike Ozgul Onal
- Department of Histology and Embryology, Faculty of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey
| | - Eyup Altinoz
- Department of Medical Biochemistry, Faculty of Medicine, Karabuk University, Karabuk, Turkey.
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25
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Delfino MM, Jampani JLDA, Lopes CS, Guerreiro-Tanomaru JM, Tanomaru-Filho M, Sasso-Cerri E, Cerri PS. Participation of fibroblast growth factor-1 and interleukin-10 in connective tissue repair following subcutaneous implantation of bioceramic materials in rats. Int Endod J 2023; 56:385-401. [PMID: 36353742 DOI: 10.1111/iej.13867] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022]
Abstract
AIM To evaluate whether the bioceramic materials Bio-C Pulpo (Bio-C, Angelus) and mineral trioxide aggregate (MTA) Repair HP (MTA-HP, Angelus) induce fibroblast proliferation and release of interleukin-10 (IL-10), an anti-inflammatory cytokine, stimulating connective tissue remodelling. The tissue response of Bio-C and MTA-HP was compared with the White MTA (WMTA; Angelus) since studies have demonstrated that WMTA induces tissue repair. METHODOLOGY Bio-C, MTA-HP and WMTA were inserted into polyethylene tubes and implanted in the subcutaneous tissue of Holtzman rats for 7, 15, 30 and 60 days. As a control group (CG), empty tubes were implanted subcutaneously. The number of fibroblasts (FB), Ki-67-, fibroblast growth factor-1- (FGF-1) and IL-10-immunolabelled cells and collagen content in the capsules was obtained. The data were subjected to two-way anova followed by Tukey's test (p ≤ .05). RESULTS At 7 days, significant differences in the number of FB were not detected amongst Bio-C, MTA-HP and WMTA groups (p ˃ .05). The capsules of all groups exhibited a significant increase in the number of FB and content of collagen over time. From 7 to 60 days, a significant reduction in the number of FGF-1- and Ki-67-immunolabelled cells was seen in the capsules of all specimens. In all periods, no significant difference in the number of FGF-1-immunolabelled cells was detected between Bio-C and CG specimens. At 60 days, significant differences in the immunoexpression of FGF-1 were not observed amongst the groups. At 7 and 15 days, the highest immunoexpression for Ki-67 was present in Bio-C specimens whilst, after 30 and 60 days, no significant difference was observed amongst the bioceramic materials. At 7 days, few IL-10 immunolabelled cells were present in the capsules of all specimens whereas, at 60 days, a significant increase in the IL-10-immunostaining was present in all groups. At 60 days, the Bio-C, MTA-HP and WMTA groups showed a greater number of IL-10-immunolabelled cells than in the CG specimens (p < .0001). CONCLUSIONS Bio-C, MTA-HP and WMTA stimulate fibroblast proliferation, leading to the formation of collagen-rich capsules. FGF-1 and IL-10 may mediate the remodelling of capsules around Bio-C, MTA-HP and WMTA bioceramic materials.
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Affiliation(s)
- Mateus Machado Delfino
- Department of Restorative Dentistry, Dental School, São Paulo State University (UNESP), Araraquara, Brazil
| | - José Leandro de Abreu Jampani
- Laboratory of Histology and Embryology, Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, Dental School, São Paulo State University (UNESP), Araraquara, Brazil
| | - Camila Soares Lopes
- Department of Restorative Dentistry, Dental School, São Paulo State University (UNESP), Araraquara, Brazil
| | | | - Mário Tanomaru-Filho
- Department of Restorative Dentistry, Dental School, São Paulo State University (UNESP), Araraquara, Brazil
| | - Estela Sasso-Cerri
- Laboratory of Histology and Embryology, Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, Dental School, São Paulo State University (UNESP), Araraquara, Brazil
| | - Paulo Sérgio Cerri
- Laboratory of Histology and Embryology, Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, Dental School, São Paulo State University (UNESP), Araraquara, Brazil
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Tarighati E, Keivan H, Mahani H. A review of prognostic and predictive biomarkers in breast cancer. Clin Exp Med 2023; 23:1-16. [PMID: 35031885 DOI: 10.1007/s10238-021-00781-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 12/01/2021] [Indexed: 12/12/2022]
Abstract
Breast cancer (BC) is a common cancer all over the world that affects women. BC is one of the leading causes of cancer mortality in women, which today has decreased with the advancement of technology and new diagnostic and therapeutic methods. BCs are histologically divided into in situ and invasive carcinoma, and both of them can be divided into ductal and lobular. The main function after the diagnosis of invasive breast cancer is which patient should use chemotherapy, which patient should receive adjuvant therapy, and which should not. If the decision is for adjuvant therapy, the next challenge is to identify the most appropriate treatment or combination of treatments for a particular patient. Addressing the first challenge can be helped by prognostic biomarkers, while addressing the second challenge can be done by predictive biomarkers. Among the molecular markers related to BC, ER, PR, HER2, and the Mib1/Ki-67 proliferation index are the most significant ones and are tightly confirmed in the standard care of all primary, recurrent, and metastatic BC patients. CEA and CA-15-3 antigens are the most valuable markers of serum tumors in BC patients. Determining the series of these markers helps monitor response to the treatment and early detection of recurrence or metastasis. miRNAs have been demonstrated to be intricate in mammary gland growth, proliferation, and formation of BC known to be incriminated in BC biology. By combining established prognostic factors with valid prognostic/predicted biomarkers, we can start the journey to personalized treatment for every recently diagnosed BC patient.
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Affiliation(s)
- Elaheh Tarighati
- Department of Medical Physics, Iran University of Medical Sciences, Tehran, Iran
| | - Hadi Keivan
- School of Paramedicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Hojjat Mahani
- Radiation Applications Research School, Nuclear Science and Technology Research Institute, P.O. Box: 14395-836, Tehran, Iran.
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He Y, Zhang J, Chen H, Zhou Y, Hong L, Ma Y, Chen N, Zhao W, Tong Z. Clinical significance and prognostic value of receptor conversion after neoadjuvant chemotherapy in breast cancer patients. Front Surg 2023; 9:1037215. [PMID: 36684294 PMCID: PMC9852345 DOI: 10.3389/fsurg.2022.1037215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/25/2022] [Indexed: 01/09/2023] Open
Abstract
The hormone receptor (HR) status and human epidermal growth hormone receptor 2 (HER2) status of patients with breast cancer may change following neoadjuvant chemotherapy (NAC). We retrospectively analyzed the clinical data of 294 patients with stage II/III breast cancer to evaluate the clinical significance and prognostic value of receptor transformation after NAC in breast cancer patients. Pathological complete response after NAC was achieved in 10.7% of patients. HR, estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 conversion rates were 9.2%, 6.5%, 13.0%, 4.4%, and 33.7%, respectively. Patients with stable HR (P = 0.01) and HER2 (P = 0.048) expression had more favorable overall survival (OS). Low or reduced Ki-67 expression was associated with better disease-free survival (DFS) (P < 0.001) and OS (P < 0.01). Multivariate analysis showed that the number of lymph nodes after NAC, HR conversion, and radiotherapy were independent prognostic factors for overall survival. HR conversion implied a higher risk of death [hazard ratio, 2.56 (95% confidence interval: 1.19-5.51); P = 0.016]. Patients with HR conversion after NAC who received endocrine therapy had better DFS (P = 0.674) and OS (P = 0.363) than those who did not receive endocrine therapy, even if the HR changed from positive to negative. In conclusion, pathological testing should be performed before and after NAC, and even patients with HR conversion after NAC might benefit from endocrine therapy.
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Affiliation(s)
- Yang He
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Breast Cancer, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Jing Zhang
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Integrative Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Hui Chen
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Oncology, Characteristic Medical Center of PAP, Tianjin, China
| | - Ying Zhou
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Integrative Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Liping Hong
- Center for Precision Cancer Medicine and Translational Research, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Yue Ma
- The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Nannan Chen
- Department of Breast Cancer, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Weipeng Zhao
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Zhongsheng Tong
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Correspondence: Zhongsheng Tong
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Dai X, Shen Y, Gao Y, Huang G, Lin B, Liu Y. Correlation study between apparent diffusion coefficients and the prognostic factors in breast cancer. Clin Radiol 2023; 78:347-355. [PMID: 36746720 DOI: 10.1016/j.crad.2022.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 11/10/2022] [Accepted: 11/17/2022] [Indexed: 01/05/2023]
Abstract
AIM To analyse the correlation between apparent diffusion coefficients (ADC) derived from intratumoural and peritumoural regions with prognostic factors and immune-inflammatory markers in breast cancer (BC). MATERIALS AND METHODS In this retrospective study, 89 patients (age range, 28-66 years; median, 45 years) with a diagnosis of invasive BC who underwent routine blood tests and multiparametric magnetic resonance imaging (MRI) were enrolled. The study cohort was stratified according to tumour maximum cross-section ≥20 mm, lymph node metastasis (LNM), time-signal intensity curve (TIC) type, and receptor status. Minimum, maximum, mean, and heterogeneity values of tumour ADC (ADCtmin, ADCtmax, ADCtmean, and ADCheter), maximum values of peritumoural ADC (ADCpmax), and the ratio of peritumoural-tumour ADC (ADCratio) were obtained on the ADC maps. Linear regression analyses were performed to investigate the correlation between immune-inflammatory markers, prognostic factors and ADC values. RESULTS HER-2 was positively associated with ADCtmax, ADCtmean, and ADCpmax values (β = 0.306, p=0.004; β = 0.283, p=0.007; β = 0.262, p=0.007, respectively), while platelet-to-lymphocyte ratio (PLR) was positively associated with ADCpmax and ADCratio values (β = 0.227, p=0.020; β = 0.231, p=0.020, respectively). Among ADC parameters, ADCpmax showed the highest predictive values for evaluating the presence of LNM (AUC, 0.751; sensitivity, 70.4%; specificity, 77.1%). CONCLUSION The ADCpmax value could provide additional assistance in predicting prognostic factors of BC.
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Affiliation(s)
- X Dai
- Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China; Department of Radiology, Longgang Central Hospital of Shenzhen, Shenzhen, China
| | - Y Shen
- Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China; Department of Radiology, Longgang Central Hospital of Shenzhen, Shenzhen, China.
| | - Y Gao
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - G Huang
- Department of Pathology, Longgang Central Hospital of Shenzhen, Shenzhen, China
| | - B Lin
- Department of Breast Surgery, Longgang Central Hospital of Shenzhen, Shenzhen, China
| | - Y Liu
- Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China; Department of Radiology, Longgang Central Hospital of Shenzhen, Shenzhen, China
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Xie B, Lin X, Wu K, Chen J, Qiu S, Luo J, Huang Y, Peng L. Adipose tissue levels of polybrominated diphenyl ethers in relation to prognostic biomarkers and progression-free survival time of breast cancer patients in eastern area of southern China: A hospital-based study. ENVIRONMENTAL RESEARCH 2023; 216:114779. [PMID: 36370816 DOI: 10.1016/j.envres.2022.114779] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 11/06/2022] [Accepted: 11/08/2022] [Indexed: 11/10/2022]
Abstract
Evidence indicates that individual or groups of polybrominated diphenyl ethers (PBDEs) are associated with risk of breast cancer (BC). Epidemiological studies of PBDEs and BC progression are scarce. This study aimed to investigate the relationships between PBDE burdens in adipose tissues and prognostic biomarkers of BC as well as progression-free survival (PFS) of patients for the first time. The concentrations of 14 PBDE congeners in breast adipose tissues of 183 cases from the eastern area of southern China were analyzed by gas chromatography-mass spectrometry (GC-MS). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models for the associations between PBDE levels and prognostic biomarkers. Kaplan-Meier and Cox regression analyses were conducted to identify the correlations between PBDEs and PFS. The results showed that BDE-99 and 190 levels were positively associated with clinical stage and N stage respectively (OR = 2.61 [1.26-5.40], OR = 2.78 [1.04-7.46]). Concentrations of BDE-28 and BDE-183 were negatively associated with the expression of estrogen receptor (ER) (OR = 0.30 [0.11-0.81]; 0.39 [0.15-0.99]) and progesterone receptor (PR) (OR = 0.36 [0.14-0.92]; 0.37 [0.15-0.91]), and increased BDE-47 was associated with lower human epidermal growth factor receptor 2 (HER2) expression (OR = 0.44 [0.23-0.86]). Adipose levels of BDE-71, 99, 138, 153, 154 and total PBDEs were positively associated with p53 expression (all P < 0.05). Finally, BDE-47, 99 and 183 were considered as independent prognostic factors for shorter PFS in the Cox models (adjusted hazard ratios = 3.14 [1.26-7.82]; 2.25 [1.03-4.94]; 2.60 [1.08-6.25], respectively). The recurrence risk and prognosis of BC may be closely bound to the body burdens of certain PBDE congeners. Further epidemiological and experimental studies are needed for confirmation.
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Affiliation(s)
- Bingmeng Xie
- Central Laboratory, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong, 515041, China; School of Public Health, Shantou University, Shantou, 515041, China.
| | - Xueqiong Lin
- Department of Laboratory Medicine, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, 515041, Shantou, Guangdong, China
| | - Kusheng Wu
- School of Public Health, Shantou University, Shantou, 515041, China
| | - Jiongyu Chen
- Central Laboratory, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong, 515041, China; Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China
| | - Shuyi Qiu
- Central Laboratory, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong, 515041, China; School of Public Health, Shantou University, Shantou, 515041, China
| | - Jianan Luo
- Central Laboratory, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong, 515041, China
| | - Yiteng Huang
- Health Care Center, First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, PR China.
| | - Lin Peng
- Central Laboratory, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong, 515041, China; Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
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Ogier du Terrail J, Leopold A, Joly C, Béguier C, Andreux M, Maussion C, Schmauch B, Tramel EW, Bendjebbar E, Zaslavskiy M, Wainrib G, Milder M, Gervasoni J, Guerin J, Durand T, Livartowski A, Moutet K, Gautier C, Djafar I, Moisson AL, Marini C, Galtier M, Balazard F, Dubois R, Moreira J, Simon A, Drubay D, Lacroix-Triki M, Franchet C, Bataillon G, Heudel PE. Federated learning for predicting histological response to neoadjuvant chemotherapy in triple-negative breast cancer. Nat Med 2023; 29:135-146. [PMID: 36658418 DOI: 10.1038/s41591-022-02155-w] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 11/23/2022] [Indexed: 01/21/2023]
Abstract
Triple-negative breast cancer (TNBC) is a rare cancer, characterized by high metastatic potential and poor prognosis, and has limited treatment options. The current standard of care in nonmetastatic settings is neoadjuvant chemotherapy (NACT), but treatment efficacy varies substantially across patients. This heterogeneity is still poorly understood, partly due to the paucity of curated TNBC data. Here we investigate the use of machine learning (ML) leveraging whole-slide images and clinical information to predict, at diagnosis, the histological response to NACT for early TNBC women patients. To overcome the biases of small-scale studies while respecting data privacy, we conducted a multicentric TNBC study using federated learning, in which patient data remain secured behind hospitals' firewalls. We show that local ML models relying on whole-slide images can predict response to NACT but that collaborative training of ML models further improves performance, on par with the best current approaches in which ML models are trained using time-consuming expert annotations. Our ML model is interpretable and is sensitive to specific histological patterns. This proof of concept study, in which federated learning is applied to real-world datasets, paves the way for future biomarker discovery using unprecedentedly large datasets.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Camille Franchet
- Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole, Toulouse, France
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Jin Y, Zhang M, Tong Y, Qiu L, Ye Y, Zhao B. DCXR promotes cell proliferation by promoting the activity of aerobic glycolysis in breast cancer. Mol Med Rep 2022; 27:31. [PMID: 36562355 PMCID: PMC9827345 DOI: 10.3892/mmr.2022.12918] [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: 04/02/2022] [Accepted: 09/13/2022] [Indexed: 12/23/2022] Open
Abstract
The function of human dicarbonyl/L‑xylulose reductase (DCXR) in the pathophysiology of breast cancer is yet to be elucidated. The present study aimed to investigate the function of DCXR in glycolysis and the cell cycle of breast cancer cells with respect to cell proliferation. Differential expressed DCXR was identified in The Cancer Genome Atlas (TCGA) database and verified in clinical breast cancer tissue. DCXR silencing and overexpression were induced by RNA interference and lentiviral vectors, respectively. Cell cycle progression, proliferation and glycolytic activity of breast cancer cells were detected by flow cytometry, Cell Counting Kit‑8 assay and chemical methods, respectively. Tumorigenicity was detected using nude mice xenograft models. The expression of DCXR was increased in TCGA breast cancer database and the function of DCXR was enriched in 'glycolysis' and 'cell cycle'. Further analysis using clinical breast cancer samples confirmed upregulation of DCXR. The silencing of DCXR suppressed proliferation and cell cycle progression of breast cancer cells and significantly decreased the capacity for glycolysis, thereby demonstrating the effect of DCXR on the function of breast cancer cells. Similar conclusions were obtained in DCXR overexpressing cells; notably, DCXR overexpression promoted proliferation, cell cycle progression at S phase and glycolysis. 2‑Deoxy‑D‑glucose inhibited the effect of DCXR on the proliferation and cell cycle progression of breast cancer cells. The present study revealed that DCXR regulated breast cancer cell cycle progression and proliferation by increasing glycolysis activity and thus may serve as an oncogene for breast cancer.
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Affiliation(s)
- Yongmei Jin
- Department of General Surgery, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Miao Zhang
- Central Laboratory, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Yang Tong
- Department of General Surgery, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Lin Qiu
- Department of General Surgery, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
| | - Ying Ye
- Central Laboratory, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China,Correspondence to: Professor Ying Ye, Central Laboratory, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong, Shanghai 200137, P.R. China, E-mail:
| | - Bin Zhao
- Department of General Surgery, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China,Professor Bin Zhao, Department of General Surgery, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong, Shanghai 200137, P.R. China, E-mail:
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Imamoglu EH, Duzcu SE. The prognostic importance of PD-L1, PTEN, PHH3, and KI-67 expressions in invasive breast carcinoma. Rev Assoc Med Bras (1992) 2022; 68:1638-1644. [PMID: 36449787 PMCID: PMC9779980 DOI: 10.1590/1806-9282.20220317] [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: 08/29/2022] [Accepted: 08/29/2022] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVE The aim of this study was to investigate the relationship of PD-L1, PTEN, PHH3, and Ki-67 immunohistochemical stain expressions with prognostic clinicopathological parameters in breast cancer. METHODS Lumpectomy and mastectomy materials from 85 patients operated at the Department of Pathology, Bolu Abant Izzet Baysal University, Faculty of Medicine between 2014 and 2019 were retrospectively reviewed. PD-L1, PTEN, PHH3, and Ki-67 expressions were examined. Immunohistochemical staining results were compared with clinicopathological parameters and found to be associated with prognosis. RESULTS A statistically significant correlation was found between PD-L1 and large tumor size, high histological grade, multifocality, and lymphovascular invasion. A statistically significant correlation was found between the loss of PTEN and large tumor size and histological grade. There was a statistically significant correlation between PHH3 and advanced age, large tumor size, and high histological grade. A statistically significant correlation was found between Ki-67 and large tumor size, high histological grade, and lymphovascular invasion. CONCLUSION PD-L1, PTEN, PHH3, and Ki-67 are regarded as potential biomarkers that can be used to predict the prognosis of breast cancer and to develop targeted therapies.
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Affiliation(s)
- Eda Hilal Imamoglu
- Bolu Abant İzzet Baysal University, Medical School, Department of Pathology – Bolu, Turkey
| | - Selma Erdogan Duzcu
- Bolu Abant İzzet Baysal University, Medical School, Department of Pathology – Bolu, Turkey.,Corresponding author:
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Hong R, Xu B. Breast cancer: an up-to-date review and future perspectives. Cancer Commun (Lond) 2022; 42:913-936. [PMID: 36074908 PMCID: PMC9558690 DOI: 10.1002/cac2.12358] [Citation(s) in RCA: 145] [Impact Index Per Article: 48.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/16/2022] [Accepted: 08/21/2022] [Indexed: 11/10/2022] Open
Abstract
Breast cancer is the most common cancer worldwide. The occurrence of breast cancer is associated with many risk factors, including genetic and hereditary predisposition. Breast cancers are highly heterogeneous. Treatment strategies for breast cancer vary by molecular features, including activation of human epidermal growth factor receptor 2 (HER2), hormonal receptors (estrogen receptor [ER] and progesterone receptor [PR]), gene mutations (e.g., mutations of breast cancer 1/2 [BRCA1/2] and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [PIK3CA]) and markers of the immune microenvironment (e.g., tumor-infiltrating lymphocyte [TIL] and programmed death-ligand 1 [PD-L1]). Early-stage breast cancer is considered curable, for which local-regional therapies (surgery and radiotherapy) are the cornerstone, with systemic therapy given before or after surgery when necessary. Preoperative or neoadjuvant therapy, including targeted drugs or immune checkpoint inhibitors, has become the standard of care for most early-stage HER2-positive and triple-negative breast cancer, followed by risk-adapted post-surgical strategies. For ER-positive early breast cancer, endocrine therapy for 5-10 years is essential. Advanced breast cancer with distant metastases is currently considered incurable. Systemic therapies in this setting include endocrine therapy with targeted agents, such as CDK4/6 inhibitors and phosphoinositide 3-kinase (PI3K) inhibitors for hormone receptor-positive disease, anti-HER2 targeted therapy for HER2-positive disease, poly(ADP-ribose) polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple-negative disease. Innovation technologies of precision medicine may guide individualized treatment escalation or de-escalation in the future. In this review, we summarized the latest scientific information and discussed the future perspectives on breast cancer.
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Affiliation(s)
- Ruoxi Hong
- Department of Medical OncologySun Yat‐Sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong510060P. R. China
| | - Binghe Xu
- State Key Laboratory of Molecular Oncology and Department of Medical OncologyCancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100006P. R. China
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Fehm TN, Welslau M, Müller V, Lüftner D, Schütz F, Fasching PA, Janni W, Thomssen C, Witzel I, Belleville E, Untch M, Thill M, Tesch H, Ditsch N, Lux MP, Aktas B, Banys-Paluchowski M, Schneeweiss A, Kolberg-Liedtke C, Hartkopf AD, Wöckel A, Kolberg HC, Harbeck N, Stickeler E. Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer. Geburtshilfe Frauenheilkd 2022; 82:912-921. [PMID: 36110894 PMCID: PMC9470293 DOI: 10.1055/a-1912-7105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 07/31/2022] [Indexed: 11/01/2022] Open
Abstract
This review summarizes recent developments in the prevention and treatment of patients with early-stage breast cancer. The individual disease risk for different molecular subtypes was investigated in a large epidemiological study. With regard to treatment, new data are available from long-term follow-up of the Aphinity study, as well as new data on neoadjuvant therapy with atezolizumab in HER2-positive patients. Biomarkers, such as residual cancer burden, were investigated in the context of pembrolizumab therapy. A Genomic Grade Index study in elderly patients is one of a group of studies investigating the use of modern multigene tests to identify patients with an excellent prognosis in whom chemotherapy may be avoided. These and other aspects of the latest developments in the diagnosis and treatment of breast cancer are described in this review.
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Affiliation(s)
- Tanja N. Fehm
- Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany
| | | | - Volkmar Müller
- Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
| | - Diana Lüftner
- Immanuel Hospital Märkische Schweiz & Medical University of Brandenburg Theodor-Fontane, Brandenburg, Buckow, Germany
| | - Florian Schütz
- Gynäkologie und Geburtshilfe, Diakonissen-Stiftungs-Krankenhaus Speyer, Speyer, Germany
| | - Peter A. Fasching
- Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen,
Germany,Correspondence/Korrespondenzadresse Peter A. Fasching, MD Erlangen University Hospital, Department of Gynecology and ObstetricsComprehensive Cancer
Center Erlangen EMNFriedrich Alexander University of Erlangen-NurembergUniversitätsstraße 21 – 2391054
ErlangenGermany
| | - Wolfgang Janni
- Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany
| | - Christoph Thomssen
- Department of Gynaecology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Isabell Witzel
- Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
| | | | - Michael Untch
- Clinic for Gynecology and Obstetrics, Breast Cancer Center, Gynecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin, Germany
| | - Marc Thill
- Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt am Main, Germany
| | - Hans Tesch
- Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany
| | - Nina Ditsch
- Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany
| | - Michael P. Lux
- Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, St. Vincenz Krankenhaus GmbH, Germany
| | - Bahriye Aktas
- Department of Gynecology, University of Leipzig Medical Center, Leipzig, Germany
| | - Maggie Banys-Paluchowski
- Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Andreas Schneeweiss
- National Center for Tumor Diseases (NCT), Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany
| | | | - Andreas D. Hartkopf
- Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany
| | - Achim Wöckel
- Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany
| | | | - Nadia Harbeck
- Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich, Germany
| | - Elmar Stickeler
- Department of Gynecology and Obstetrics, RWTH University Hospital Aachen, Aachen, Germany
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Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway. Int J Mol Sci 2022; 23:ijms231810362. [PMID: 36142286 PMCID: PMC9499653 DOI: 10.3390/ijms231810362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/30/2022] [Accepted: 09/02/2022] [Indexed: 12/23/2022] Open
Abstract
We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin’s anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. We found that cordycepin reduced the volume and weight of MDA-MB-231 xenografts and affected the expression of proliferation-, apoptosis-, epithelial–mesenchymal transition-, and matrix metalloproteinase-related proteins without side effects. RNA sequencing screening, pathway enrichment, and the protein network interaction analysis revealed enriched pathways and targets mainly concentrated on the Hedgehog pathway and its core components of SHH and GLI2. This indicates that the Hedgehog pathway plays a central role in the cordycepin-mediated regulation of growth and metastasis formation in TNBC. The database analysis of the Hedgehog pathway markers (SHH, PTCH1, SMO, GLI1, and GLI2) revealed that the Hedgehog pathway is activated in breast cancer tissues, and its high expression is not conducive to a patient’s survival. Finally, we verified that cordycepin effectively inhibited the Hedgehog pathway in TNBC through Western blotting and immunohistochemistry. This study found that cordycepin could regulate the growth and metastasis formation of TNBC through the Hedgehog pathway in vivo, which provides new insights for targeting and treating breast cancer.
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dos Santos A, Ouellete G, Diorio C, Elowe S, Durocher F. Knockdown of CKAP2 Inhibits Proliferation, Migration, and Aggregate Formation in Aggressive Breast Cancer. Cancers (Basel) 2022; 14:cancers14153759. [PMID: 35954424 PMCID: PMC9367390 DOI: 10.3390/cancers14153759] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 11/26/2022] Open
Abstract
Simple Summary Cancer is a complex disease where cells grow and divide in an uncontrolled manner. It is well established that its development and progression involve major alterations in the activity of mitotic regulators. In order to improve our understanding of the contribution of cell-cycle progression defects to the development of disease, the aim of this study is to identify genes relevant to the proper progression of mitosis that are deregulated in breast cancer. Our findings identified CKAP2 as an important mitotic regulator in BC tumors. Moreover, in vitro experiments showed that gene silencing of CKAP2 blocked cell growth, cell migration, and formation of cell aggregates. These results demonstrated the important role of CKAP2 in breast cancer tumor formation. Abstract Loss of mitotic regulation is commonly observed in cancer and is a major cause of whole-chromosome aneuploidy. The identification of genes that play a role in the proper progression of mitosis can help us to understand the development and evolution of this disease. Here, we generated a list of proteins implicated in mitosis that we used to probe a patient-derived breast cancer (BC) continuum gene-expression dataset generated by our group by human transcriptome analysis of breast lesions of varying aggressiveness (from normal to invasive). We identified cytoskeleton-associated protein 2 (CKAP2) as an important mitotic regulator in invasive BC. The results showed that CKAP2 is overexpressed in invasive BC tumors when compared with normal tissues, and highly expressed in all BC subtypes. Higher expression of CKAP2 is also related to a worse prognosis in overall survival and relapse-free survival in estrogen receptor (ER)-positive and human epidermal growth factor receptor type 2 (HER2)-negative BC patients. Knockdown of CKAP2 in SKBR3 cells impaired cell proliferation and cell migration and reduced aggregate formation in a 3D culture. Our results show the important role of CKAP2 in BC tumorigenesis, and its potential utility as a prognostic marker in BC.
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Affiliation(s)
- Alexsandro dos Santos
- Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Québec City, QC G1V 0A6, Canada; (A.d.S.); (G.O.)
- Centre de Recherche sur le Cancer, CHU de Québec-Université Laval, Québec City, QC G1V 4G2, Canada;
- PROTEO-Regroupement Québécois de Recherche sur la Fonction, L’ingénierie et les Applications des Protéines, Québec City, QC G1V 0A6, Canada
| | - Geneviève Ouellete
- Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Québec City, QC G1V 0A6, Canada; (A.d.S.); (G.O.)
- Centre de Recherche sur le Cancer, CHU de Québec-Université Laval, Québec City, QC G1V 4G2, Canada;
| | - Caroline Diorio
- Centre de Recherche sur le Cancer, CHU de Québec-Université Laval, Québec City, QC G1V 4G2, Canada;
- Département de Médecine Sociale et Préventive, Faculté de Médecine, Université Laval, Québec City, QC G1V 0A6, Canada
| | - Sabine Elowe
- Centre de Recherche sur le Cancer, CHU de Québec-Université Laval, Québec City, QC G1V 4G2, Canada;
- PROTEO-Regroupement Québécois de Recherche sur la Fonction, L’ingénierie et les Applications des Protéines, Québec City, QC G1V 0A6, Canada
- Département de Pédiatrie, Faculté de Médecine, Université Laval et le Centre de recherche sur le Cancer de l’Université Laval, Québec City, QC G1R 2J6, Canada
- Correspondence: (S.E.); (F.D.)
| | - Francine Durocher
- Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Québec City, QC G1V 0A6, Canada; (A.d.S.); (G.O.)
- Centre de Recherche sur le Cancer, CHU de Québec-Université Laval, Québec City, QC G1V 4G2, Canada;
- Correspondence: (S.E.); (F.D.)
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Liu Q, Qiu J, Lu Q, Ma Y, Fang S, Bu B, Song L. Comparison of endocrine therapy and chemotherapy as different systemic treatment modes for metastatic luminal HER2-negative breast cancer patients —A retrospective study. Front Oncol 2022; 12:873570. [PMID: 35957911 PMCID: PMC9360505 DOI: 10.3389/fonc.2022.873570] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeThe purpose of this study was to evaluate endocrine therapy and chemotherapy for first-line, maintenance, and second-line treatment of hormone receptor-positive HER-2-negative metastatic breast cancer (HR+HER-2-MBC) and the relationship between different treatment options and survival.Patients and methodsThe patients included in this study were all diagnosed with metastatic breast cancer (MBC) at Shandong Cancer Hospital from January 2013 to June 2017. Of the 951 patients with MBC, 307 patients with HR+HER-2-MBC were included in the analysis. The progression-free survival (PFS) and overall survival (OS) of the various treatment modes were evaluated using Kaplan–Meier analysis and the log-rank test. Because of the imbalance in data, we used the synthetic minority oversampling technique (SMOTE) algorithm to oversample the data to increase the balanced amount of data.ResultsThis retrospective study included 307 patients with HR+HER-2-MBC; 246 patients (80.13%) and 61 patients (19.87%) were treated with first-line chemotherapy and first-line endocrine therapy, respectively. First-line endocrine therapy was better than first-line chemotherapy in terms of PFS and OS. After adjusting for known prognostic factors, patients receiving first-line chemotherapy had poorer PFS and OS outcomes than patients receiving first-line endocrine therapy. In terms of maintenance treatment, the endocrine therapy-endocrine therapy maintenance mode achieved the best prognosis, followed by the chemotherapy-endocrine therapy maintenance mode and chemotherapy-chemotherapy maintenance mode, and the no-maintenance mode has resulted in the worst prognosis. In terms of first-line/second-line treatment, the endocrine therapy/endocrine therapy mode achieved the best prognosis, while the chemotherapy/chemotherapy mode resulted in the worst prognosis. The chemotherapy/endocrine therapy mode achieved a better prognosis than the endocrine therapy/chemotherapy mode. There were no significant differences in the KI-67 index (<15%/15-30%/≥30%) among the patients receiving first-line treatment modes, maintenance treatment modes, and first-line/second-line treatment modes. There was no statistical evidence in this study to support that the KI-67 index affected survival. However, in the first-line/second-line model, after SMOTE, we could see that KI-67 ≥ 30% had a poor prognosis.ConclusionsDifferent treatment modes for HR+HER-2-MBC were analyzed. Endocrine therapy achieved better PFS and OS outcomes than chemotherapy. Endocrine therapy should be the first choice for first-line, maintenance, and second-line treatment of HR+HER-2-MBC.
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Affiliation(s)
- Qiuyue Liu
- Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China
| | - Juan Qiu
- Oncology Department, The Fourth People’s Hospital of Jinan, Jinan, China
| | - Qianrun Lu
- Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China
| | - Yujin Ma
- Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China
| | - Shu Fang
- Department of Breast Medicine, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China
| | - Bing Bu
- Department of Breast Medicine, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China
| | - Lihua Song
- Department of Breast Medicine, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China
- *Correspondence: Lihua Song,
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Vasselli F, Fabi A, Ferranti FR, Barba M, Botti C, Vidiri A, Tommasin S. How Dual-Energy Contrast-Enhanced Spectral Mammography Can Provide Useful Clinical Information About Prognostic Factors in Breast Cancer Patients: A Systematic Review of Literature. Front Oncol 2022; 12:859838. [PMID: 35941874 PMCID: PMC9355886 DOI: 10.3389/fonc.2022.859838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 05/27/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction In the past decade, a new technique derived from full-field digital mammography has been developed, named contrast-enhanced spectral mammography (CESM). The aim of this study was to define the association between CESM findings and usual prognostic factors, such as estrogen receptors, progesterone receptors, HER2, and Ki67, in order to offer an updated overview of the state of the art for the early differential diagnosis of breast cancer and following personalized treatments. Materials and Methods According to the PRISMA guidelines, two electronic databases (PubMed and Scopus) were investigated, using the following keywords: breast cancer AND (CESM OR contrast enhanced spectral mammography OR contrast enhanced dual energy mammography) AND (receptors OR prognostic factors OR HER2 OR progesterone OR estrogen OR Ki67). The search was concluded in August 2021. No restriction was applied to publication dates. Results We obtained 28 articles from the research in PubMed and 114 articles from Scopus. After the removal of six replicas that were counted only once, out of 136 articles, 37 articles were reviews. Eight articles alone have tackled the relation between CESM imaging and ER, PR, HER2, and Ki67. When comparing radiological characterization of the lesions obtained by either CESM or contrast-enhanced MRI, they have a similar association with the proliferation of tumoral cells, as expressed by Ki-67. In CESM-enhanced lesions, the expression was found to be 100% for ER and 77.4% for PR, while moderate or high HER2 positivity was found in lesions with non-mass enhancement and with mass closely associated with a non-mass enhancement component. Conversely, the non-enhancing breast cancer lesions were not associated with any prognostic factor, such as ER, PR, HER2, and Ki67, which may be associated with the probability of showing enhancement. Radiomics on CESM images has the potential for non-invasive characterization of potentially heterogeneous tumors with different hormone receptor status. Conclusions CESM enhancement is associated with the proliferation of tumoral cells, as well as to the expression of estrogen and progesterone receptors. As CESM is a relatively young imaging technique, a few related works were found; this may be due to the “off-label” modality. In the next few years, the role of CESM in breast cancer diagnostics will be more thoroughly investigated.
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Affiliation(s)
- Federica Vasselli
- Radiology and Diagnostic Imaging, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Alessandra Fabi
- Precision Medicine in Breast Cancer Unit, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Francesca Romana Ferranti
- Radiology and Diagnostic Imaging, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Maddalena Barba
- Division of Medical Oncology 2, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Claudio Botti
- Division of Breast Surgery, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Antonello Vidiri
- Radiology and Diagnostic Imaging, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
- *Correspondence: Antonello Vidiri,
| | - Silvia Tommasin
- Human Neuroscience Department, Sapienza University of Rome, Rome, Italy
- Neuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Rome, Italy
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Reolão BR, Mora DS, Garcia MCDS, Bonamigo RR. Breast carcinoma metastasis and Wolf's isotopic response. An Bras Dermatol 2022; 97:467-470. [PMID: 35676106 PMCID: PMC9263666 DOI: 10.1016/j.abd.2021.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 10/11/2021] [Accepted: 10/24/2021] [Indexed: 11/29/2022] Open
Abstract
Wolf's isotopic phenomenon occurs when a new dermatosis appears on a site that has already healed from a previous dermatological disease of another etiology. This report describes the case of a 44-year-old female patient undergoing treatment for breast carcinoma who recently had brownish erythematous lesions appearing on the scar region of previous herpes zoster on the right hemithorax. Histopathology and immunohistochemistry examination confirmed skin metastasis of breast cancer. Herpes zoster scars require attention due to the possibility of an isotopic response as a facilitating factor in some dermatoses, sometimes severe ones, such as neoplasms.
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Affiliation(s)
| | | | | | - Renan Rangel Bonamigo
- Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil; Ambulatório de Dermatologia Sanitária do Rio Grande do Sul, Porto Alegre, RS, Brazil; Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Amezcua‑Gálvez J, Lopez‑Garcia C, Villarreal‑Garza C, Lopez‑Rivera V, Canavati‑Marcos M, Santuario‑Facio S, Dono A, Monroig‑Bosque P, Ortiz‑López R, Leal‑Lopez A, Gómez‑macías G. Concordance between Ki‑67 index in invasive breast cancer and molecular signatures: EndoPredict and MammaPrint. Mol Clin Oncol 2022; 17:132. [PMID: 35949891 PMCID: PMC9353786 DOI: 10.3892/mco.2022.2565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 02/17/2022] [Indexed: 12/24/2022] Open
Abstract
Identifying patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who benefit from adjuvant chemotherapy has improved with molecular signature tests. However, due to high cost and limited availability, alternative tests are used. The present study sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. From the San José TecSalud Hospital in Monterrey México, patients with HR+ EIBC as tested with EndoPredict or MammaPrint and Ki-67 index were identified. They were categorized into two groups: Group 1 (June 2016-August 2018) was evaluated using EndoPredict and Group 2 (June 2016-August 2018) with MammaPrint. A ≥20% Ki67 index cutoff was utilized to identify highly proliferative EIBC and an area under the receiver-operating characteristic curve and κ concordance were utilized to evaluate the performance of Ki-67 index compared to molecular signature tests. In the EndoPredict group, 54/96 patients were considered high-risk based on their EPclin score, while 57/96 patients had Ki-67 index ≥20%. However, there was no significant overall concordance between them (59.37%, κ=0.168, P=0.09), while the given risk of distant recurrence given in percentage by EPclin had a positive association with the Ki67 index (P=0.04). In the MammaPrint group, 21/70 patients were considered high-risk and 36/70 patients presented with a Ki-67 index ≥20% with a significant overall concordance (67.14%, κ=0.35, P<0.001). In addition, high Ki-67 index was associated with the Nottingham histological grade in both groups. In conclusion, there was a concordance between Ki-67 and MammaPrint risk stratification of HR+ EIBC and no concordance with the EndoPredict molecular signature, but a positive association with the given percentage of recurrence and the median Ki-67 index as the cutoff at our center. Cost-effectiveness analyses of these tests in developing countries are required; until then, the use of Ki-67 appears reasonable to aid clinical decisions, together with the other established clinicopathological variables.
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Affiliation(s)
- Jesús Amezcua‑Gálvez
- Department of Pathology, Tecnologico de Monterrey, Hospital San José, Av. Morones Prieto Poniente 3000 Poniente, Los Doctores, Monterrey, NL 64710, México
| | - Carlos Lopez‑Garcia
- Department of Pathology, Tecnologico de Monterrey, Hospital San José, Av. Morones Prieto Poniente 3000 Poniente, Los Doctores, Monterrey, NL 64710, México
| | - Cynthia Villarreal‑Garza
- Breast Cancer Center, Tecnologico de Monterrey, Hospital Zambrano Hellion, Real San Agustín, San Pedro Garza García, NL 66278, México
| | - Victor Lopez‑Rivera
- Department of Neurology, UTHealth McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77030, USA
| | - Mauricio Canavati‑Marcos
- Breast Cancer Center, Tecnologico de Monterrey, Hospital Zambrano Hellion, Real San Agustín, San Pedro Garza García, NL 66278, México
| | - Sandra Santuario‑Facio
- School of Medicine and Health Sciences, Tecnologico de Monterrey, Av Morones Prieto, 3000 Poniente, Los Doctores, Monterrey, Nuevo León, 64710, México
| | - Antonio Dono
- Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77030, USA
| | - Paloma Monroig‑Bosque
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Rocío Ortiz‑López
- School of Medicine and Health Sciences, Tecnologico de Monterrey, Av Morones Prieto, 3000 Poniente, Los Doctores, Monterrey, Nuevo León, 64710, México
| | - Andrea Leal‑Lopez
- Breast Cancer Center, Tecnologico de Monterrey, Hospital Zambrano Hellion, Real San Agustín, San Pedro Garza García, NL 66278, México
| | - Gabriela Gómez‑macías
- Department of Pathology, Tecnologico de Monterrey, Hospital San José, Av. Morones Prieto Poniente 3000 Poniente, Los Doctores, Monterrey, NL 64710, México
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Tang L, Wei X, Li C, Dai J, Bai X, Mao L, Chi Z, Cui C, Lian B, Tang B, Du Y, Wang X, Lai Y, Sheng X, Yan X, Li S, Zhou L, Kong Y, Li Z, Si L, Guo J. Proliferation Marker Ki67 as a Stratification Index of Adjuvant Chemotherapy for Resectable Mucosal Melanoma. Front Oncol 2022; 12:895672. [PMID: 35847851 PMCID: PMC9280123 DOI: 10.3389/fonc.2022.895672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 06/09/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundAdjuvant chemotherapy has been shown to produce a favorable prognosis for patients with resectable mucosal melanoma (MM), resulting in the need for stratification to optimally select patients to benefit from adjuvant therapy. This study analyzed Ki67 as a potential stratification index for adjuvant chemotherapy in resectable MM.MethodsPatients with resected MM who received subsequent adjuvant therapy in Beijing Cancer Hospital between 2010 and 2018 were retrospectively enrolled and analyzed. Relapse-free survival (RFS) and melanoma-specific survival (MSS) curves were used to perform the survival comparisons across different subgroups.ResultsFrom Jan 2010 to Dec 2018, 1106 MM patients were screened from a database of 4706 patients and 175 of these patients were finally enrolled. A total of 100 patients received temozolomide (TMZ)-based adjuvant chemotherapy and 75 patients received high-dose interferon-α2b (HDI) adjuvant therapy. Compared with HDI, patients who received TMZ-based adjuvant chemotherapy had significantly superior RFS (21.0 vs. 9.6 months, P = 0.002). For patients with low Ki67 expression (<30%), the two regimens showed no significant difference for impact on RFS (33.9 vs. 22.7 months, P = 0.329). However, for patients with high Ki67 expression (≥30%), TMZ-based adjuvant chemotherapy achieved favorable RFS compared with HDI (18.0 vs. 6.7 months, P < 0.001) and tended to improve MSS compared to HDI (41.4 vs. 25.1 months, P = 0.067).ConclusionCompared with HDI, adjuvant chemotherapy may be more relevant for patients with Ki67 ≥ 30%. Ki67 may serve as a potential index to distinguish populations benefiting from adjuvant chemotherapy in resectable MM, and may provide a basis for stratification in the selection of adjuvant regimens.
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Affiliation(s)
- Lirui Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiaoting Wei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Caili Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jie Dai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xue Bai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Lili Mao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhihong Chi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Chuanliang Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Bin Lian
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Bixia Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yu Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xuan Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yumei Lai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xinan Sheng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Cancers, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xieqiao Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Cancers, Peking University Cancer Hospital and Institute, Beijing, China
| | - Siming Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Cancers, Peking University Cancer Hospital and Institute, Beijing, China
| | - Li Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Cancers, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yan Kong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China
- *Correspondence: Jun Guo, ; Lu Si, ; Zhongwu Li,
| | - Lu Si
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
- *Correspondence: Jun Guo, ; Lu Si, ; Zhongwu Li,
| | - Jun Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Cancers, Peking University Cancer Hospital and Institute, Beijing, China
- *Correspondence: Jun Guo, ; Lu Si, ; Zhongwu Li,
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Rossi V, Govoni M, Farabegoli F, Di Stefano G. Lactate is a potential promoter of tamoxifen resistance in MCF7 cells. Biochim Biophys Acta Gen Subj 2022; 1866:130185. [PMID: 35661802 DOI: 10.1016/j.bbagen.2022.130185] [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: 02/08/2022] [Revised: 05/05/2022] [Accepted: 05/31/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND Tamoxifen is a widely used estrogen receptor inhibitor, whose clinical success is limited by the development of acquired resistance. This compound was also found to inhibit mitochondrial function, causing increased glycolysis and lactate production. Lactate has been widely recognized as a signaling molecule, showing the potential of modifying gene expression. These metabolic effects of tamoxifen can by hypothesized to contribute in driving drug resistance. METHODS To test this hypothesis, we used MCF7 cells together with a tamoxifen resistant cell line (MCF7-TAM). Experiments were aimed at verifying whether enhanced lactate exposure can affect the phenotype of MCF7 cells, conferring them features mirroring those observed in the tamoxifen resistant culture. RESULTS The obtained results suggested that enhanced lactate in MCF7 cells medium can increase the expression of tafazzin (TAZ) and telomerase complex (TERC, TERT) genes, reducing the cells' attitude to undergo senescence. In long term lactate-exposed cells, signs of EGFR activation, a pathway related to acquired tamoxifen resistance, was also observed. CONCLUSIONS The obtained results suggested lactate as a potential promoter of tamoxifen resistance. The off-target effects of this compound could play a role in hindering its therapeutic efficacy. GENERAL SIGNIFICANCE The features of acquired tamoxifen resistance have been widely characterized at the molecular level; in spite of their heterogeneity, poorly responsive cells were often found to display upregulated glycolysis. Our results suggest that this metabolic asset is not simply a result of neoplastic progression, but can play an active part in driving this process.
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Affiliation(s)
- Valentina Rossi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy
| | - Marzia Govoni
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy
| | - Fulvia Farabegoli
- Department of Pharmacy and Biotechnology, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy
| | - Giuseppina Di Stefano
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
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Ma ST, Wang DY, Liu YB, Tan HJ, Ge YY, Chi Y, Zhang BL. Prognostic factors of primary neuroendocrine breast cancer: A population-based study. Cancer Med 2022; 11:2533-2540. [PMID: 35499193 PMCID: PMC9249978 DOI: 10.1002/cam4.4557] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 09/09/2021] [Accepted: 12/30/2021] [Indexed: 11/06/2022] Open
Abstract
Background Primary neuroendocrine breast carcinomas (NEBCs) are an extremely rare and underrecognized subtype of mammalian carcinoma. The prognostic factors for NEBCs remain controversial. Methods In this multicenter retrospective study, the prognostic factors for patients with primary NEBCs who underwent surgery and had a pathologically confirmed diagnosis of neuroendocrine carcinoma in China and the United States were examined. The endpoints were disease‐free survival (DFS) and overall survival (OS). Results A total of 51 Chinese patients and 98 US patients were included. In the Chinese cohort, tumor grade and Ki‐67 levels were prognostic factors for DFS in univariate analysis (hazard ratio [HR] = 5.11 [1.67–15.60], p = 0.004; HR = 57.70 [6.36–523.40], p < 0.001, respectively) and multivariate analysis (HR = 100.52 [1.33–7570.21], p = 0.037; HR = 31.47 [1.05–945.82], p = 0.047, respectively). In the US cohort, age was an important prognostic factor for OS in univariate analysis (HR = 1.09 [1.04–1.15], p = 0.001). The random effects model for the combined cohorts revealed age and positive expression of estrogen receptor (ER) as potential prognostic factors for OS (HR = 1.08 [1.01–1.14], p = 0.015; HR = 0.10 [0.02–0.44], p = 0.003, respectively). Conclusions Tumor grade and Ki‐67 levels are important prognostic factors for DFS of patients with primary NEBCs. Age and ER status are important prognostic factors for OS of patients with primary NEBCs.
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Affiliation(s)
- Shu-Tao Ma
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ding-Yuan Wang
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi-Bing Liu
- Third Clinical Medical College, Jilin University, Changchun, China
| | - Hui-Jing Tan
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue-Yue Ge
- Department of Geriatric Medicine, National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Chinese Academy of Medical Sciences, Beijing, China
| | - Yihebali Chi
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bai-Lin Zhang
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Massafra R, Bove S, La Forgia D, Comes MC, Didonna V, Gatta G, Giotta F, Latorre A, Nardone A, Palmiotti G, Quaresmini D, Rinaldi L, Tamborra P, Zito A, Rizzo A, Fanizzi A, Lorusso V. An Invasive Disease Event-Free Survival Analysis to Investigate Ki67 Role with Respect to Breast Cancer Patients' Age: A Retrospective Cohort Study. Cancers (Basel) 2022; 14:2215. [PMID: 35565344 PMCID: PMC9104454 DOI: 10.3390/cancers14092215] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/21/2022] [Accepted: 04/27/2022] [Indexed: 02/01/2023] Open
Abstract
Characterization of breast cancer into intrinsic molecular profiles has allowed women to live longer, undergoing personalized treatments. With the aim of investigating the relation between different values of ki67 and the predisposition to develop a breast cancer-related IDE at different ages, we enrolled 900 patients with a first diagnosis of invasive breast cancer, and we partitioned the dataset into two sub-samples with respect to an age value equal to 50 years. For each sample, we performed a Kaplan−Meier analysis to compare the IDE-free survival curves obtained with reference to different ki67 values. The analysis on patients under 50 years old resulted in a p-value < 0.001, highlighting how the behaviors of patients characterized by a ki67 ranging from 10% to 20% and greater than 20% were statistically significantly similar. Conversely, patients over 50 years old characterized by a ki67 ranging from 10% to 20% showed an IDE-free survival probability significantly greater than patients with a ki67 greater than 20%, with a p-value of 0.01. Our work shows that the adoption of two different ki67 values, namely, 10% and 20%, might be discriminant in designing personalized treatments for patients under 50 years old and over 50 years old, respectively.
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Affiliation(s)
- Raffaella Massafra
- Struttura Semplice Dipartimentale di Fisica Sanitaria, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (R.M.); (S.B.); (V.D.); (P.T.); (A.F.)
| | - Samantha Bove
- Struttura Semplice Dipartimentale di Fisica Sanitaria, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (R.M.); (S.B.); (V.D.); (P.T.); (A.F.)
| | - Daniele La Forgia
- Struttura Semplice Dipartimentale di Radiologia Senologica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy;
| | - Maria Colomba Comes
- Struttura Semplice Dipartimentale di Fisica Sanitaria, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (R.M.); (S.B.); (V.D.); (P.T.); (A.F.)
| | - Vittorio Didonna
- Struttura Semplice Dipartimentale di Fisica Sanitaria, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (R.M.); (S.B.); (V.D.); (P.T.); (A.F.)
| | - Gianluca Gatta
- Dipartimento di Medicina di Precisione, Università degli Studi della Campania “Luigi Vanvitelli”, 80131 Napoli, Italy;
| | - Francesco Giotta
- Unità Operativa Complessa di Oncologia Medica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (F.G.); (A.L.); (V.L.)
| | - Agnese Latorre
- Unità Operativa Complessa di Oncologia Medica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (F.G.); (A.L.); (V.L.)
| | - Annalisa Nardone
- Unità Opertiva Complessa di Radioterapia, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy;
| | - Gennaro Palmiotti
- Struttura Semplice Dipartimentale di Oncologia Per la Presa in Carico Globale del Paziente, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (G.P.); (L.R.); (A.R.)
| | - Davide Quaresmini
- Unità Operativa Complessa di Oncologia Medica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (F.G.); (A.L.); (V.L.)
| | - Lucia Rinaldi
- Struttura Semplice Dipartimentale di Oncologia Per la Presa in Carico Globale del Paziente, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (G.P.); (L.R.); (A.R.)
| | - Pasquale Tamborra
- Struttura Semplice Dipartimentale di Fisica Sanitaria, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (R.M.); (S.B.); (V.D.); (P.T.); (A.F.)
| | - Alfredo Zito
- Unità Operativa Complessa di Anatomia Patologica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy;
| | - Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Per la Presa in Carico Globale del Paziente, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (G.P.); (L.R.); (A.R.)
| | - Annarita Fanizzi
- Struttura Semplice Dipartimentale di Fisica Sanitaria, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (R.M.); (S.B.); (V.D.); (P.T.); (A.F.)
| | - Vito Lorusso
- Unità Operativa Complessa di Oncologia Medica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (F.G.); (A.L.); (V.L.)
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Botticelli A, Fabbri A, Roberto M, Alesini D, Cirillo A, D'Auria G, Krasniqi E, Marrucci E, Muratore M, Pantano F, Pizzuti L, Portarena I, Rossi R, Scagnoli S, Marchetti P. The Role of the CDK4/6 Inhibitor Ribociclib in Locally Advanced and Oligometastatic Hormone Receptor Positive, Her2 Negative, Advanced Breast Cancer: Case Series and Review of the Literature. Front Oncol 2022; 12:797157. [PMID: 35223478 PMCID: PMC8864134 DOI: 10.3389/fonc.2022.797157] [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: 10/18/2021] [Accepted: 01/12/2022] [Indexed: 11/13/2022] Open
Abstract
The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors to endocrine therapy has remarkably improved the outcome of patients affected with hormone receptor positive (HR+), human epidermal grow factor receptor 2 negative (HER2 -) advanced breast cancer (ABC). Ribociclib showed to be effective across most subgroups, regardless of the number and the site of metastasis. Up to 10% of patients with ABC, reported an oligometastatic condition, recently defined as a slow-volume metastatic disease with limited number and size of metastatic lesions (up to 5 and not necessarily in the same organ), potentially amenable for local treatment, aimed at achieving a complete remission status. Despite the wide use of CDK4/6 inhibitors in HR+, HER2-, ABC treatment, data regarding both locally advanced, inoperable disease and oligometastatic conditions are still poor. We reported a review and case series of HR+, HER2-, ABC patients treated with ribociclib as first-line therapy, for a locally advanced and oligometastatic conditions, reporting an impressive response and good safety profile.
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Affiliation(s)
- Andrea Botticelli
- Medical Oncology Unit B, Policlinico Umberto I, Rome, Italy.,Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant'Andrea Hospital, Rome, Italy
| | - Agnese Fabbri
- Medical Oncology Unit, Belcolle Hospital, Viterbo, Italy
| | - Michela Roberto
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant'Andrea Hospital, Rome, Italy.,Medical Oncology Unit A, Policlinico Umberto I, Rome, Italy
| | - Daniele Alesini
- UOSD Centro Oncologico S. Spirito e Nuovo Regina Margherita (SS-NRM), Ospedale Santo Spirito in Sassia, Rome, Italy
| | - Alessio Cirillo
- Medical Oncology Unit B, Policlinico Umberto I, Rome, Italy.,Department of Radiological, Oncological and Anatomo-Pathological Science, "Sapienza" University of Rome, Rome, Italy
| | - Giuliana D'Auria
- Department of Medical Oncology, Sandro Pertini Hospital, Rome, Italy
| | - Eriseld Krasniqi
- Division of Medical Oncology 2, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | | | - Margherita Muratore
- Division of Gynecologic Oncology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy
| | - Francesco Pantano
- Department of Oncology, University Campus Biomedico of Rome, Rome, Italy
| | - Laura Pizzuti
- Division of Medical Oncology 2, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Ilaria Portarena
- Medical Oncology Unit, Internal Medicine Department, Tor Vergata Clinical Center University Hospital, Rome, Italy
| | - Rosalina Rossi
- Medical Oncology, San Giovanni Addolorata Hospital, Rome, Italy
| | - Simone Scagnoli
- Medical Oncology Unit B, Policlinico Umberto I, Rome, Italy.,Department of Medical and Surgical Sciences and Translational Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Paolo Marchetti
- Medical Oncology Unit B, Policlinico Umberto I, Rome, Italy.,Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant'Andrea Hospital, Rome, Italy
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Liu C, Zhou J, Chang C, Zhi W. Feasibility of Shear Wave Elastography Imaging for Evaluating the Biological Behavior of Breast Cancer. Front Oncol 2022; 11:820102. [PMID: 35155209 PMCID: PMC8830494 DOI: 10.3389/fonc.2021.820102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 12/30/2021] [Indexed: 12/27/2022] Open
Abstract
Objective To explore the feasibility of shear wave elastography (SWE) parameters for assessing the biological behavior of breast cancer. Materials and Methods In this prospective study, 224 breast cancer lesions in 216 female patients were examined by B-mode ultrasound and shear wave elastography in sequence. The maximum size (Smax) of the lesion was measured by B-mode ultrasound, and then shear wave elastography was performed on this section to obtain relevant parameters, including maximum elasticity (Emax), mean elasticity (Emean), standard deviation of elasticity (SD), and the area ratio of shear wave elastography to B-mode ultrasound (AR). The relationship between SWE parameters and pathological type, histopathological classification, histological grade, lymphovascular invasion status (LVI), axillary lymph node status (ALN), and immunohistochemistry of breast cancer lesions was performed according to postoperative pathology. Results In the univariate analysis, the pathological type and histopathological classification of breast cancer were not significantly associated with SWE parameters; with an increase in the histological grade of invasive ductal carcinoma (IDC), SD (p = 0.016) and Smax (p = 0.000) values increased. In the ALN-positive group, Smax (p = 0.004) was significantly greater than in the ALN-negative group; Smax (p = 0.003), Emax (p = 0.034), and SD (p = 0.045) were significantly higher in the LVI-positive group than in the LVI-negative group; SD (p = 0.043, p = 0.047) and Smax (p = 0.000, p = 0.000) were significantly lower in the ER+ and PR+ groups than in the ER- and PR- groups, respectively; AR (p = 0.032) was significantly higher in the ER+ groups than in the ER- groups, and Smax (p = 0.002) of the HER2+ group showed higher values than that of the HER2- group; Smax (p = 0.000), SD (p = 0.006), and Emax (p = 0.004) of the Ki-67 high-expression group showed significantly higher values than those of the Ki-67 low-expression group. In the multivariate analysis, Ki-67 was an independent factor of Smax (p = 0.005), Emax (p = 0.004), and SD (p = 0.006); ER was an independent influencing factor of Smax (p = 0.000) and AR (p = 0.032). LVI independently influences Smax (p = 0.006). Conclusions The SWE parameters Emax, SD, and AR can be used to evaluate the biological behavior of breast cancer.
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Affiliation(s)
- Chaoxu Liu
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jin Zhou
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Cai Chang
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenxiang Zhi
- Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
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Zhu M, Chen L, Kong X, Wang X, Li X, Fang Y, Wang J. The Systemic Immune-Inflammation Index is an Independent Predictor of Survival in Breast Cancer Patients. Cancer Manag Res 2022; 14:775-820. [PMID: 35241935 PMCID: PMC8887616 DOI: 10.2147/cmar.s346406] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 01/11/2022] [Indexed: 12/13/2022] Open
Abstract
Purpose The current investigation examines the potential clinical value and prognostic significance of a systemic immune-inflammation index (SII) in patients with breast cancer. Patients and Methods A total of 477 individuals underwent neoadjuvant chemotherapy, and 308 individuals did not at our center between January 1998 and December 2016 were selected. An optimized SII threshold was generated using a receiver operating characteristic curve (ROC). The relationship between various factors and breast cancer in predicting disease-free survival (DFS) and overall survival (OS) were analyzed. Results The SII < 560 group (Low SII group) and SII ≥ 560 group (High SII group) are divided according to the threshold value. SII was an independent predictor for breast cancer DFS and OS based on univariate and multivariate analyses. Low SII patients had higher mean DFS and OS in contrast to those in the high SII groups (46.65 vs 27.37 months and 69.92 vs 49.53 months). Those in the low SII cohort who also had early or advanced breast cancer, different molecular subtypes, and with or without lymph vessel invasion all had higher mean survival time of DFS and OS in contrast to those with raised SII values (P<0.05). The mean DFS and OS durations also varied based on different Miller and Payne grades (MPG) (P <0.005), and different response groups (P<0.05). Conclusion SII can be used as an easily accessible and minimally invasive potential prognostic factor in individuals with breast cancer and may also guide clinicians in treating and prognosticating patients with breast cancer.
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Affiliation(s)
- Mengliu Zhu
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Li Chen
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China
| | - Xiangyi Kong
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Xiangyu Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Xingrui Li
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China
| | - Yi Fang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Jing Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
- Correspondence: Jing Wang; Yi Fang, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email ;
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Ki-67 and breast cancer prognosis: does it matter if Ki-67 level is examined using preoperative biopsy or postoperative specimen? Breast Cancer Res Treat 2022; 192:343-352. [PMID: 35025005 PMCID: PMC8926964 DOI: 10.1007/s10549-022-06519-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 01/04/2022] [Indexed: 11/17/2022]
Abstract
Purpose This study aimed to identify the association between Ki-67 level and the prognosis of patients with breast cancer, regardless of the timing of Ki-67 testing (using preoperative biopsy vs. postoperative specimen). Methods A total of 4177 patients underwent surgery between January 2008 and December 2016. Immunohistochemical Ki-67 levels, using either preoperative (1673) or postoperative (2831) specimens, were divided into four groups using cutoff points of 10%, 15%, and 20%. Results Groups with higher-Ki-67 levels, in both the pre- and postoperative periods, showed significantly larger tumor size, higher grade, more frequent hormone receptor-negativity and human epidermal growth factor receptor 2 overexpression, and active adjuvant treatments than groups with lower-Ki-67 levels. High-Ki-67 levels were also significantly associated with poor survival, irrespective of the timing of specimen examination. Conclusion Despite the problems associated with Ki-67, Ki-67 level is an important independent prognostic factor, regardless of the timing of Ki-67 testing, i.e., preoperative or postoperative testing.
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Chen J, Li CX, Shao SH, Yao MH, Su YJ, Wu R. The association between conventional ultrasound and contrast-enhanced ultrasound appearances and pathological features in small breast cancer. Clin Hemorheol Microcirc 2021; 80:413-422. [PMID: 34842181 DOI: 10.3233/ch-211291] [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] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To investigate the association between ultrasound appearances and pathological features in small breast cancer. MATERIALS AND METHODS A total of 186 small breast cancers in 186 patients were analyzed in this retrospective study from January 2015 to December 2019 according to pathological results. Forty-seven cases of axillary lymph node metastasis were found. All patients underwent radical axillary surgery following conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations. The association between ultrasound appearances and pathological features was analyzed using univariate distributions and multivariate analysis. Then, a logistic regression model was established using the pathological diagnosis of lymph node metastasis and biochemical indicators as the dependent variable and the ultrasound appearances as independent variables. RESULTS In small breast cancer, risk factors of axillary lymph node metastasis were crab claw-like enhancement on CEUS and abnormal axillary lymph nodes on US. The logistic regression model was established as follows: (axillary lymph node metastasis) = 1.100×(crab claw-like enhancement of CEUS) + 2.749×(abnormal axillary lymph nodes of US) -5.790. In addition, irregular shape on CEUS and posterior echo attenuation on US were risk factors for both positive estrogen receptor and progesterone receptor expression, whereas calcification on US was a risk factor for positive Her-2 expression. A specific relationship could be found using the following logistic models: (positive ER expression) = 1.367×(irregular shape of CEUS) + 1.441×(posterior echo attenuation of US) -5.668; (positive PR expression) = 1.265×(irregular shape of CEUS) + 1.136×(posterior echo attenuation of US) -4.320; (positive Her-2 expression) = 1.658×(calcification of US) -0.896. CONCLUSION Logistic models were established to provide significant value for the prediction of pre-operative lymph node metastasis and positive biochemical indicators, which may guide clinical treatment.
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Affiliation(s)
- Jing Chen
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chun-Xiao Li
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Si-Hui Shao
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming-Hua Yao
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi-Jin Su
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rong Wu
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Patel P, Shah J. Protective effects of hesperidin through attenuation of Ki67 expression against DMBA-induced breast cancer in female rats. Life Sci 2021; 285:119957. [PMID: 34530017 DOI: 10.1016/j.lfs.2021.119957] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 08/31/2021] [Accepted: 09/08/2021] [Indexed: 12/24/2022]
Abstract
AIMS Doxorubicin (Dox) is routinely used for breast cancer treatment but toxicity and drug resistance limit its use. The objective of the study was to investigate the protective effects of hesperidin alone and in combination with doxorubicin against experimentally induced breast cancer in female rats. METHODS Breast cancer (BC) was induced by administration of 7,12-dimethylbenz(a)anthracene (DMBA) through subcutaneous injection into the 3rd right mammary gland of female Wistar rats. Hesperidin (Hes) pretreated groups were started with Hes (200 mg/kg) two weeks prior to DMBA induction. Animals were randomly divided into nine groups namely vehicle control, DMBA-induced, Dox 4 mg/kg, Dox 2 mg/kg, Hes (200 mg/kg), Hes (200 mg/kg) plus Dox 4 mg/kg treated groups and Hes pretreated groups treated with DMBA, Dox 4 mg/kg and Dox 2 mg/kg. KEY FINDINGS Hes pretreated groups showed reduced tumor occurrence, tumor volume and increased survival rate as compared to DMBA-induced group of animals. Hes pretreated animals treated with Dox 4 mg/kg and 2 mg/kg exhibited significant reduction in malondialdehyde and improvement in levels of glutathione and inflammatory markers like IL-6, TNF-α, NF-κB, IFN-γ as compared to Dox 4 mg/kg and 2 mg/kg treated animals. Histopathology and Ki67 expression depicted better control of tumor with Hes pretreatment groups as compared to DMBA-induced. Histopathology of vital organs of Hes pretreated groups treated with Dox revealed lesser toxicity than Dox treated groups. SIGNIFICANCE Hesperidin possesses protective effect against experimentally induced breast cancer in female rats that appears to be related to attenuation of Ki67 expression.
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Affiliation(s)
- Pankti Patel
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India
| | - Jigna Shah
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India.
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