{"title":"Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case-control study within the E3N-Generations cohort.","authors":"Benoît Mercoeur, Béatrice Fervers, Thomas Coudon, Hwayoung Noh, Camille Giampiccolo, Lény Grassot, Elodie Faure, Florian Couvidat, Gianluca Severi, Francesca Romana Mancini, Pascal Roy, Delphine Praud, Amina Amadou","doi":"10.1186/s13058-024-01913-7","DOIUrl":"10.1186/s13058-024-01913-7","url":null,"abstract":"<p><strong>Background: </strong>Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO<sub>2</sub>), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk.</p><p><strong>Methods: </strong>We used data from a nested case-control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects).</p><p><strong>Results: </strong>The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)<sub>Q4 vs Q1</sub> = 2.32, 95% confidence intervals (CI): 1.00-5.37). PCB153 exposure showed a positive association only in the third quartile (OR<sub>Q3 vs Q1</sub> = 2.25, CI 1.13-4.57), but it appeared to be non-significant in the highest quartile (OR<sub>Q4 vs Q1</sub> = 2.07, CI 0.93-4.61). No association was observed between NO<sub>2</sub> exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05-1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75-1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol.</p><p><strong>Conclusion: </strong>Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"159"},"PeriodicalIF":7.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Body mass index and breast cancer risk in premenopausal and postmenopausal East Asian women: a pooled analysis of 13 cohort studies.","authors":"Keiko Wada, Koshi Kuboyama, Sarah Krull Abe, Md Shafiur Rahman, Md Rashedul Islam, Eiko Saito, Chisato Nagata, Norie Sawada, Akiko Tamakoshi, Xiao-Ou Shu, Ritsu Sakata, Atsushi Hozawa, Seiki Kanemura, Hidemi Ito, Yumi Sugawara, Sue K Park, Sun-Seog Kweon, Ayami Ono, Takashi Kimura, Wanqing Wen, Isao Oze, Min-Ho Shin, Aesun Shin, Jeongseon Kim, Jung Eun Lee, Keitaro Matsuo, Nathaniel Rothman, You-Lin Qiao, Wei Zheng, Paolo Boffetta, Manami Inoue","doi":"10.1186/s13058-024-01907-5","DOIUrl":"10.1186/s13058-024-01907-5","url":null,"abstract":"<p><strong>Background: </strong>It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women.</p><p><strong>Methods: </strong>Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China. Participants' height and weight were obtained by measurement or self-reports at cohort baseline. Breast cancer was defined as code C50.0-C50.9 according to the International Classification. Using a Cox proportional hazards model, hazard ratios of breast cancer were estimated for each body mass index category, with the reference group set as the group with a body mass index of 21 to < 23 kg/m<sup>2</sup>. The hazard ratio for a 5 kg/m<sup>2</sup> increase in body mass index was also calculated.</p><p><strong>Results: </strong>During a mean 16.6 years of follow-up, 4819 women developed breast cancer. Similar to Westerners, a steady increase in breast cancer risk with increasing body mass index was observed in postmenopausal women, but the slope of the risk increase appeared to slow at a body mass index of 26-28 kg/m<sup>2</sup>. In premenopausal women, the inverse association seen in Westerners was not observed. The risk of developing breast cancer after 50 years of age increased slightly with increasing body mass index, which was more pronounced in the older birth cohort. There was no significant association between body mass index and the risk of developing breast cancer before 50 years of age, but the risk estimates changed from positive to negative as the birth cohort got younger.</p><p><strong>Conclusions: </strong>In East Asia, the role of body mass index in breast cancer in premenopausal women may be changing along with the increase in obesity and breast cancer. The increased risk of postmenopausal breast cancer with a higher body mass index was as robust as that of Western women.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"158"},"PeriodicalIF":7.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lang Xiong, Xiaofeng Tang, Xinhua Jiang, Haolin Chen, Binyan Qian, Biyun Chen, Xiaofeng Lin, Jianhua Zhou, Li Li
{"title":"Automatic segmentation-based multi-modal radiomics analysis of US and MRI for predicting disease-free survival of breast cancer: a multicenter study.","authors":"Lang Xiong, Xiaofeng Tang, Xinhua Jiang, Haolin Chen, Binyan Qian, Biyun Chen, Xiaofeng Lin, Jianhua Zhou, Li Li","doi":"10.1186/s13058-024-01909-3","DOIUrl":"10.1186/s13058-024-01909-3","url":null,"abstract":"<p><strong>Background: </strong>Several studies have confirmed the potential value of applying radiomics to predict prognosis of breast cancer. However, the tumor segmentation in these studies depended on delineation or annotation of breast cancer by radiologist, which is often laborious, tedious, and vulnerable to inter- and intra-observer variability. Automatic segmentation is expected to overcome this difficulty. Herein, we aim to investigate the value of automatic segmentation-based multi-modal radiomics signature and magnetic resonance imaging (MRI) features in predicting disease-free survival (DFS) of patients diagnosed with invasive breast cancer.</p><p><strong>Methods: </strong>This retrospective multicenter study included a total of 643 female patients with invasive breast cancer who underwent preoperative ultrasound (US) and MRI for prognostic analysis. Data (n = 480) from center 1 were divided into training and internal testing sets, while data (n = 163) from centers 2 and 3 were analyzed as the external testing set. We developed automatic segmentation frameworks for tumor segmentation by deep learning. Then, Least absolute shrinkage and selection operator Cox regression was used to select features to construct radiomics signature, and corresponding radiomics score (Rad-score) was calculated. Finally, six models for predicting DFS were constructed by using Cox regression and assessed in terms of discrimination, calibration, and clinical usefulness.</p><p><strong>Results: </strong>The multi-modal radiomics signature combining intra- and peri-tumoral radiomics signatures of US and MRI achieved a higher C-index in the internal (0.734) and external (0.708) testing sets than most other radiomics signatures in predicting DFS, and successfully stratified patients into low- and high-risk groups. The multi-modal clinical imaging model combining the multi-modal Rad-score and clinical traditional MRI model-score resulted in a higher C-index (0.795) than other models in the external testing set, and it had a better calibration and higher clinical benefit.</p><p><strong>Conclusions: </strong>This study demonstrates that the multi-modal radiomics signature derived from automatic segmentations of US and MRI is a promising risk stratification biomarker for breast cancer, and highlights that the appropriate combination of multi-modal radiomics signature, clinical characteristics, and MRI feature can improve performance of individualized DFS prediction, which might assist in guiding decision-making related to breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"157"},"PeriodicalIF":7.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conrad Lee, Heilum Yip, Joshua J X Li, Joanna Ng, Julia Y Tsang, Thomson Loong, Gary M Tse
{"title":"Clinical values of nuclear morphometric analysis in fibroepithelial lesions.","authors":"Conrad Lee, Heilum Yip, Joshua J X Li, Joanna Ng, Julia Y Tsang, Thomson Loong, Gary M Tse","doi":"10.1186/s13058-024-01912-8","DOIUrl":"10.1186/s13058-024-01912-8","url":null,"abstract":"<p><strong>Background: </strong>Fibroepithelial lesions (FELs) of the breast encompass a broad spectrum of lesions, ranging from commonly encountered fibroadenomas (FAs) to rare phyllodes tumors (PTs). Accurately diagnosing and grading these lesions is crucial for making management decisions, but it can be challenging due to their overlapping features and the subjective nature of histological assessment. Here, we evaluated the role of digital nuclear morphometric analysis in FEL diagnosis and prognosis.</p><p><strong>Methods: </strong>A digital nuclear morphometric analysis was conducted on 241 PTs and 59 FAs. Immunohistochemical staining for cytokeratin and Leukocyte common antigen (LCA) was used to exclude non-stromal components, and nuclear area, perimeters, calipers, circularity, and eccentricity in the stromal cells were quantified with QuPath software. The correlations of these features with FEL diagnosis and prognosis was assessed.</p><p><strong>Results: </strong>All nuclear features, including area, perimeter, circularity, maximum caliper, minimum caliper and eccentricity, showed significant differences between FAs and benign PTs (p ≤ 0.002). Only nuclear area, perimeter, minimum caliper and eccentricity correlated significantly with PT grading (p ≤ 0.022). For differentiation of FAs from benign PTs, the model integrating all differential nuclear features demonstrated a specificity of 90% and sensitivity of 70%. For PT grading, the nuclear morphometric score showed a specificity of 78% and sensitivity of 96% for distinguishing benign/borderline from malignant PTs. In addition, a relationship of nuclear circularity was found with PT recurrence. The Kaplan-meier analysis, using the best cutoff determined by ROC curve, showed shorter event free survival in benign PTs with high circularity (chi-square = 4.650, p = 0.031).</p><p><strong>Conclusions: </strong>Our data suggested the digital nuclear morphometric analysis could have potentials to objectively differentiate different FELs and predict PT outcome. These findings could provide the evidence-based data to support the development of deep-learning based algorithm on nuclear morphometrics in FEL diagnosis.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"156"},"PeriodicalIF":7.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jasmine M Manouchehri, Jharna Datta, Lynn M Marcho, Jesse J Reardon, Daniel Stover, Robert Wesolowski, Uma Borate, Ting-Yuan David Cheng, Patrick M Schnell, Bhuvaneswari Ramaswamy, Gina M Sizemore, Mark P Rubinstein, Mathew A Cherian
{"title":"The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer.","authors":"Jasmine M Manouchehri, Jharna Datta, Lynn M Marcho, Jesse J Reardon, Daniel Stover, Robert Wesolowski, Uma Borate, Ting-Yuan David Cheng, Patrick M Schnell, Bhuvaneswari Ramaswamy, Gina M Sizemore, Mark P Rubinstein, Mathew A Cherian","doi":"10.1186/s13058-024-01906-6","DOIUrl":"10.1186/s13058-024-01906-6","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer, one of the most common forms of cancer, is associated with the highest cancer-related mortality among women worldwide. In comparison to other types of breast cancer, patients diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst outcome because current therapies do not produce long-lasting responses. Hence, innovative therapies that produce persisting responses are a critical need. We previously discovered that hyperactivating purinergic receptors (P2RXs) by increasing extracellular adenosine triphosphate (eATP) concentrations enhances TNBC cell lines' response to chemotherapy. Heparan sulfate inhibits multiple extracellular ATPases, so it is a molecule of interest in this regard. In turn, heparanase degrades polysulfated polysaccharide heparan sulfate. Importantly, previous work suggests that breast cancer and other cancers express heparanase at high levels. Hence, as heparan sulfate can inhibit extracellular ATPases to facilitate eATP accumulation, it may intensify responses to chemotherapy. We postulated that heparanase inhibitors would exacerbate chemotherapy-induced decreases in TNBC cell viability by increasing heparan sulfate in the cellular microenvironment and hence, augmenting eATP.</p><p><strong>Methods: </strong>We treated TNBC cell lines MDA-MB 231, Hs 578t, and MDA-MB 468 and non-tumorigenic immortal mammary epithelial MCF-10A cells with paclitaxel (cytotoxic chemotherapeutic) with or without the heparanase inhibitor OGT 2115 and/or supplemental heparan sulfate. We evaluated cell viability and the release of eATP. Also, we compared the expression of heparanase protein in cell lines and tissues by immunoblot and immunohistochemistry, respectively. In addition, we examined breast-cancer-initiating cell populations using tumorsphere formation efficiency assays on treated cells.</p><p><strong>Results: </strong>We found that combining heparanase inhibitor OGT 2115 with chemotherapy decreased TNBC cell viability and tumorsphere formation through increases in eATP and activation of purinergic receptors as compared to TNBC cells treated with single-agent paclitaxel.</p><p><strong>Conclusion: </strong>Our data shows that by preventing heparan sulfate breakdown, heparanase inhibitors make TNBC cells more susceptible to chemotherapy by enhancing eATP concentrations.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"153"},"PeriodicalIF":7.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoonwon Kook, Young-Jin Lee, Chihhao Chu, Ji Soo Jang, Seung Ho Baek, Soong June Bae, Yoon Jin Cha, Gyungyup Gong, Joon Jeong, Sae Byul Lee, Sung Gwe Ahn
{"title":"Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 h + HER2- breast cancer: a retrospective analysis.","authors":"Yoonwon Kook, Young-Jin Lee, Chihhao Chu, Ji Soo Jang, Seung Ho Baek, Soong June Bae, Yoon Jin Cha, Gyungyup Gong, Joon Jeong, Sae Byul Lee, Sung Gwe Ahn","doi":"10.1186/s13058-024-01911-9","DOIUrl":"10.1186/s13058-024-01911-9","url":null,"abstract":"<p><strong>Background: </strong>HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.</p><p><strong>Methods: </strong>A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX<sup>®</sup> test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed.</p><p><strong>Results: </strong>Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups.</p><p><strong>Conclusion: </strong>Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"154"},"PeriodicalIF":7.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PTPN20 promotes metastasis through activating NF-κB signaling in triple-negative breast cancer.","authors":"Xiaoxiao Zuo, Xiaohan Zhao, Xiaofei Zhang, Qingyuan Li, Xingyu Jiang, Shumei Huang, Xuwei Chen, Xiangfu Chen, Weihua Jia, Hequn Zou, Dongni Shi, Xueke Qian","doi":"10.1186/s13058-024-01910-w","DOIUrl":"10.1186/s13058-024-01910-w","url":null,"abstract":"<p><strong>Background: </strong>Cancer metastasis remains a major challenge in the clinical management of triple-negative breast cancer (TNBC). The NF-κB signaling pathway has been implicated as a crucial factor in the development of metastases, but the underlying molecular mechanisms remain largely unclear.</p><p><strong>Methods: </strong>PTPN20 expression was evaluated using data from the Sweden Cancerome Analysis Network-Breast and The Cancer Genome Atlas database, as well as by western blotting and immunohistochemistry in 88 TNBC patients. The ability of PTPN20 to activate NF-κB was assessed by luciferase reporter assays. The effects of PTPN20 overexpression and knockdown via short hairpin RNA were examined in TNBC cell lines by wound healing and transwell matrix penetration assays. Additionally, we analyzed the growth and metastasis abilitiy of 4T1 xenograft tumors in nude mice.</p><p><strong>Results: </strong>PTPN20 levels were elevated in TNBC cell lines and patient samples compared to controls, and higher protein levels correlated with metastasis-free survival. Overexpression of PTPN20 enhanced migration and invasion in vitro, and promoted lung metastasis in vivo. Our finding revealed that PTPN20 activates NF-κB signaling by dephosphorylating p65 at Ser468, preventing its binding to COMMD1, thereby protecting p65 from degradation. Downregulation of PTPN20 effectively inhibit, while p65 S468A mutant restored the migratory and invasive abilities of TNBC cells.</p><p><strong>Conclusions: </strong>Collectively, our results demonstrate that PTPN20 plays a critical role in TNBC metastasis through the activation of NF-κB signaling. We propose that PTPN20 may serve as a novel prognostic marker and potential therapeutic target for the treatment of TNBC.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"155"},"PeriodicalIF":7.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Young Joo Lee, Woo Chul Noh, Sungchan Gwark, Hyun-Ah Kim, Jai Min Ryu, Seung Il Kim, Eun-Gyeong Lee, Seock-Ah Im, Yongsik Jung, Min Ho Park, Kyong Hwa Park, Su Hwan Kang, Joon Jeong, Eunhwa Park, Sung Yong Kim, Min Hyuk Lee, Lee Su Kim, Woosung Lim, Seonok Kim, Hee Jeong Kim
{"title":"Prediction of menstrual recovery patterns in premenopausal women with breast cancer taking tamoxifen after chemotherapy: an ASTRRA Substudy.","authors":"Young Joo Lee, Woo Chul Noh, Sungchan Gwark, Hyun-Ah Kim, Jai Min Ryu, Seung Il Kim, Eun-Gyeong Lee, Seock-Ah Im, Yongsik Jung, Min Ho Park, Kyong Hwa Park, Su Hwan Kang, Joon Jeong, Eunhwa Park, Sung Yong Kim, Min Hyuk Lee, Lee Su Kim, Woosung Lim, Seonok Kim, Hee Jeong Kim","doi":"10.1186/s13058-024-01903-9","DOIUrl":"10.1186/s13058-024-01903-9","url":null,"abstract":"<p><strong>Background: </strong>Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients.</p><p><strong>Methods: </strong>In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels.</p><p><strong>Results: </strong>The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age (< 35 vs. 45, HR 7.85, 95% CI 4.63-13.30, p < 0.0001), anthracycline-based chemotherapy without taxane (vs. with taxane, HR 1.81, 95% CI 1.37-2.38, p < 0.0001), and chemotherapy duration (≤ 90 days vs. > 90 days, HR 1.32, 95% CI 1.01-1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation.</p><p><strong>Conclusion: </strong>This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"152"},"PeriodicalIF":7.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marit Busund, Giske Ursin, Eiliv Lund, Sairah Lai Fa Chen, Charlotta Rylander
{"title":"Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study.","authors":"Marit Busund, Giske Ursin, Eiliv Lund, Sairah Lai Fa Chen, Charlotta Rylander","doi":"10.1186/s13058-024-01897-4","DOIUrl":"10.1186/s13058-024-01897-4","url":null,"abstract":"<p><strong>Background: </strong>Menopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.</p><p><strong>Methods: </strong>Data from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.</p><p><strong>Results: </strong>MHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36-1.52), 1.41 (95% CI 1.31-1.52), and 1.23 (95% CI 1.09-1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36-1.91) and 2.15% (95% CI 1.51-3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24-0.73 among current users). Results varied significantly according to tumor subtype (p<sub>heterogeneity</sub> = 0.02).</p><p><strong>Conclusions: </strong>Our study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"151"},"PeriodicalIF":7.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Hornstrup Christensen, Christina Anne Vinter, Thomas Bastholm Olesen, Maria Houborg Petersen, Ellen Aagaard Nohr, Katrine Hass Rubin, Marianne Skovsager Andersen, Dorte Moeller Jensen
{"title":"Breast cancer in women with previous gestational diabetes: a nationwide register-based cohort study.","authors":"Maria Hornstrup Christensen, Christina Anne Vinter, Thomas Bastholm Olesen, Maria Houborg Petersen, Ellen Aagaard Nohr, Katrine Hass Rubin, Marianne Skovsager Andersen, Dorte Moeller Jensen","doi":"10.1186/s13058-024-01908-4","DOIUrl":"10.1186/s13058-024-01908-4","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk.</p><p><strong>Methods: </strong>We conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test.</p><p><strong>Results: </strong>Of 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83-1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk.</p><p><strong>Conclusions: </strong>This large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"150"},"PeriodicalIF":7.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}