Breast Cancer Research and Treatment最新文献

{"title":"National trends and survival outcomes associated with non-guideline-concordant treatment of inflammatory breast cancer.","authors":"Elsa A Kronen, Nikhil L Chervu, Ayesha P Ng, Hanjoo Lee, Peyman Benharash, Carlie K Thompson","doi":"10.1007/s10549-025-07669-8","DOIUrl":"https://doi.org/10.1007/s10549-025-07669-8","url":null,"abstract":"<p><strong>Purpose: </strong>National Comprehensive Cancer Network (NCCN) guidelines for inflammatory breast cancer (IBC) recommend trimodal therapy: neoadjuvant chemotherapy, modified radical mastectomy (MRM), and adjuvant radiation therapy. Historically, a minority received NCCN-guideline-concordant trimodal therapy (GCT). We explored factors associated with non-concordance, types of non-concordance, and the association of GCT with survival.</p><p><strong>Methods: </strong>The National Cancer Database (NCDB) was analyzed for patients with non-metastatic IBC who underwent surgery from 2006 to 2019. Multivariate logistic regression identified factors associated with GCT. Cox proportional hazard models assessed the impact of GCT, and components of non-concordance, on mortality.</p><p><strong>Results: </strong>Of 13,733 patients, 47.6% received GCT. Of non-GCT patients, 39.7% had mixed non-concordance, 25.5% exclusive chemotherapy non-concordance, 24.0% exclusive radiation non-concordance, and 10.8% exclusive surgical non-concordance. A higher burden of comorbidities, node-negative disease, and positive human epidermal growth factor receptor 2 (HER2) and hormone receptor status were associated with reduced odds of receiving GCT. GCT was associated with reduced 3-(hazard ratio [HR] = 0.83, 95% CI 0.73-0.95) and 5-year (HR = 0.83, 95% CI 0.76-0.91) mortality. Chemotherapy non-concordance and mixed non-concordance were associated with higher three-(HR = 1.28, 95% CI 1.07-1.53; HR = 1.20, 95% CI 1.01-1.43 respectively) and 5-year (HR = 1.42, 95% CI 1.26-1.60; HR = 1.17, 95% CI 1.03-1.33) mortality. Radiation non-concordance was associated with increased hazard of 1-year mortality (HR = 3.03, 95% CI 1.75-5.23). Exclusive surgical non-concordance was not associated with survival; however, simple mastectomy portended a higher hazard of 5-year mortality (HR = 1.26, 95% CI 1.08-1.46).</p><p><strong>Conclusion: </strong>Despite improved survival, a minority of patients received GCT. Omitting neoadjuvant chemotherapy or adjuvant radiation was associated with reduced survival, whereas surgical non-concordance in patients with concordant chemoradiation did not impact survival. Simple mastectomy was associated with reduced survival, supporting the rationale for axillary lymphadenectomy.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting \"don't eat me\" signal: breast cancer immunotherapy.","authors":"Yue Gao, Xiaoyan Zhang, Mingqiang Ding, Zhenkun Fu, Lei Zhong","doi":"10.1007/s10549-025-07659-w","DOIUrl":"https://doi.org/10.1007/s10549-025-07659-w","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer ranks as the most prevalent cancer type impacting women globally, both in terms of incidence and mortality rates, making it a major health concern for females. There's an urgent requirement to delve into new cancer treatment methods to improve patient survival rates.</p><p><strong>Methods: </strong>Immunotherapy has gained recognition as a promising area of research in the treatment of breast cancer, with targeted immune checkpoint therapies demonstrating the potential to yield sustained clinical responses and improve overall survival rates. Presently, the predominant immune checkpoints identified on breast cancer cells include CD47, CD24, PD-L1, MHC-I, and STC-1, among others. Nevertheless, the specific roles of these various immune checkpoints in breast carcinogenesis, metastasis, and immune evasion have yet to be comprehensively elucidated. We conducted a comprehensive review of the existing literature pertaining to breast cancer and immune checkpoint inhibitors, providing a summary of findings and an outlook on future research directions.</p><p><strong>Results: </strong>This article reviews the advancements in research concerning each immune checkpoint in breast cancer and their contributions to immune evasion, while also synthesizing immunotherapy strategies informed by these mechanisms. Furthermore, it anticipates future research priorities, thereby providing a theoretical foundation to guide immunotherapy as a potential interventional approach for breast cancer treatment.</p><p><strong>Conclusion: </strong>Knowledge of immune checkpoints will drive the creation of novel cancer therapies, and future breast cancer research will increasingly emphasize personalized treatments tailored to patients' specific tumor characteristics.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical treatment score post-5 years and survival benefit from extended endocrine therapy for breast cancer patients under and over 50 years of age.","authors":"Jee Hyun Ahn, Suk Jun Lee, Seung Hye Yang, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park","doi":"10.1007/s10549-025-07679-6","DOIUrl":"https://doi.org/10.1007/s10549-025-07679-6","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to determine whether clinical treatment score post-5 years (CTS5) could predict the clinical benefits of extended endocrine therapy (ExET) in young and old patients.</p><p><strong>Methods: </strong>We reviewed 2495 hormone receptor-positive breast cancer patients treated between 2001 and 2012 who were free from recurrence or death during the 5 years post-surgery in South Korea. The cohort was analyzed separately based on age (≤ 50 years and > 50 years). Multivariable analysis was conducted, and a cutoff of CTS5 < 3.13 was defined as the low group and CTS5 ≥ 3.13 as the intermediate/high (int/high) group.</p><p><strong>Results: </strong>The median follow-up duration was 115 months. Regardless of young and old age at diagnosis, the low group displayed considerably enhanced disease-free survival. Multivariate analysis revealed that the low group emerged as an independent and favorable prognostic factor for disease-free survival after adjusting for ExET use and prognostic parameters. Patients in the low group demonstrated a trend toward improved overall survival compared to those in the int/high group, reaching marginal statistical significance. ExET use demonstrated a significant correlation with improved disease-free survival, particularly in patients aged ≤ 50 years.</p><p><strong>Conclusions: </strong>ExET should be considered in premenopausal and postmenopausal breast cancer patients with high CTS5 levels.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR4 in endocrine resistance: overexpression and estrogen regulation without direct causative role.","authors":"Kai Ding, Lyuqin Chen, Kevin M Levine, Matthew J Sikora, Nilgun Tasdemir, David Dabbs, Rachel Jankowitz, Rachel Hazan, Osama Shah, Jenny Atkinson, Adrian V Lee, Steffi Oesterreich","doi":"10.1007/s10549-025-07666-x","DOIUrl":"https://doi.org/10.1007/s10549-025-07666-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Endocrine therapy resistance is the major challenge of managing patients with estrogen receptor positive (ER+) breast cancer. We previously reported frequent overexpression of FGFR4 in endocrine-resistant cell lines and breast cancers that recurred and metastasized following endocrine therapy, suggesting FGFR4 as a potential driver of endocrine resistance. In this study, we investigated the role of FGFR4 in mediating endocrine resistance and explored the therapeutic potential of targeting FGFR4 in advanced breast cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A gene expression signature of FGFR4 activity was examined in ER+breast cancer pre- and post-neoadjuvant endocrine therapy and the association between FGFR4 expression and patient survival was examined. A correlation analysis was used to uncover potential regulators of FGFR4 overexpression. To investigate if FGFR4 is necessary to drive endocrine resistance, we tested response to FGFR4 inhibition in long-term estrogen-deprived (LTED) cells and their paired parental cells. Doxycycline inducible FGFR4 overexpression and knockdown cell models were generated to examine if FGFR4 was sufficient to confer endocrine resistance. Finally, we examined response to FGFR4 monotherapy or combination therapy with fulvestrant in breast cancer cell lines to explore the potential of FGFR4 targeted therapy for advanced breast cancer and assessed the importance of PAM50 subtype in response to FGFR4 inhibition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A FGFR4 activity gene signature was significantly upregulated post-neoadjuvant aromatase inhibitor treatment, and high FGFR4 expression predicted poorer survival in patients with ER+breast cancer. Gene expression association analysis using TCGA, METABRIC, and SCAN-B datasets uncovered ER as the most significant gene negatively correlated with FGFR4 expression. ER negatively regulates FGFR4 expression at both the mRNA and protein level across multiple ER+breast cancer cell lines. Despite robust overexpression of FGFR4, LTED cells did not show enhanced responses to FGFR4 inhibition compared to parental cells. Similarly, FGFR4 overexpression and knockdown did not substantially alter response to endocrine treatment in ER+cell lines, nor did FGFR4 and fulvestrant combination treatment show synergistic effects. The HER2-like subtype of breast cancer showed elevated expression of FGFR4 and an increased response to FGFR4 inhibition relative to other breast cancer subtypes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Despite ER-mediated upregulation of FGFR4 post-endocrine therapy, our study does not support a general role of FGFR4 in mediating endocrine resistance in ER+breast cancer. The significant upregulation of FGFR4 expression in treatment-resistant clinical samples and models following endocrine therapy does not necessarily establish a causal link between the gene and treatment response. Our data suggest that specific genomic backgrounds such as HER2 expression m","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative radiotherapy improves long-term survival in HER2-positive metastatic breast cancer: real-world evidence from the latest SEER database.","authors":"Ling-Xiao Xie, Yang Liu, Yao-Guo Yang, Jing-Nan Wang, Yan-Qun Zhang, Tao Wang, Lu-Yang Bian, Hao Jiang, Xiao-Ming Su, Yong-Chun Zhou","doi":"10.1007/s10549-025-07665-y","DOIUrl":"https://doi.org/10.1007/s10549-025-07665-y","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the role of Postoperative Radiotherapy (PORT) in HER2-positive metastatic breast cancer (MBC) in the context of targeted therapy and clarify the subgroups that may benefit from PORT.</p><p><strong>Methods: </strong>Clinical data of female patients with HER2-positive MBC from the surveillance, epidemiology, and end results (SEER) database for the years 2016-2020 were collected according to established inclusion and exclusion criteria. The impact of PORT on patient survival was assessed, and subgroup analyses were performed to identify populations with potential benefits from PORT.</p><p><strong>Results: </strong>A total of 541 patients from the SEER database were included in the analysis. The 3-year overall survival (OS) of the PORT group was significantly higher than that of the non-PORT group. (86.7% vs. 80.2%, P = 0.011). Multivariate analysis revealed that race and PORT were independent prognostic factors. Black patients and those who received PORT had longer overall survival (OS) (P < 0.05). Subgroup analysis suggested that PORT further improved OS in patients with mastectomy, advanced TN stage, high tumor grade, positive hormone receptor status, and multiple metastatic organs (P < 0.05).</p><p><strong>Conclusion: </strong>PORT further improves the survival of HER2-positive MBC. Subgroup analysis suggests that patients with locally advanced stage (T3-4, N2-3), Grade III, HR-positive status, bone-and-visceral metastasis, and those who have undergone mastectomy benefit significantly.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the potential mediators of pathological complete response to neoadjuvant chemotherapy among TACR1 gene polymorphisms: a study on breast cancer patients.","authors":"Marziyeh Ghorbani, Soha Namazi, Mehdi Dehghani, Farideh Razi, Bahman Khalvati, Ali Dehshahri","doi":"10.1007/s10549-025-07674-x","DOIUrl":"https://doi.org/10.1007/s10549-025-07674-x","url":null,"abstract":"<p><strong>Purpose: </strong>Recent studies have shown that the truncated isoform of the neurokinin-1 receptor (NK-1R) and its ligand, substance P (SP), are overexpressed in tumor cells playing a crucial role in chemoresistance, leading to proliferation, angiogenesis, and metastasis. Hence, this study aims to assess if the polymorphisms of the NK-1R-encoding gene influence the truncated NK-1R level, chemoresistance, and pathological complete response (pCR) achievement in breast cancer patients.</p><p><strong>Methods: </strong>The real-time PCR-HRMA was performed to genotype TACR1 eighteen tag SNPs in 153 neoadjuvant chemotherapy-receiving breast cancer patients. Univariate analysis was performed to assess the association of baseline and tumor characteristics with pCR achievement. The association of each variant and pCR achievement was assessed by executing logistic regression while adjusting for covariates and correcting for multiple tests using permutation.</p><p><strong>Results: </strong>The probability of pCR to neoadjuvant chemotherapy is higher for patients with tumor grade-III as well as stage-I. Assuming the additive, dominant, or recessive models, rs17010664, rs6715729, and rs3771869 were significantly associated with pCR achievement.</p><p><strong>Conclusion: </strong>Positioned close to the truncation-occurring region, belonging to an exon-splicing enhancer motif, the rs17010664 C allele seems to play a crucial role in enhancing the TACR1 last exon splicing leading to increased truncated NK-1R production, chemoresistance, and decreased pCR achievement. Accordingly, The SP/truncated NK-1R axis blockade by NK-1R antagonists seems to be a therapeutic approach to overcoming chemoresistance and achieving pCR in the rs17010664 risk-allele-bearing patients. Hence, conducting further studies to determine the required dose of NK-1R antagonists, repurposed as an antitumor agent, is favored.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating PREDICT and developing outcome prediction models in early-onset breast cancer using data from Alberta, Canada.","authors":"Robert B Basmadjian, Yuan Xu, May Lynn Quan, Sasha Lupichuk, Winson Y Cheung, Darren R Brenner","doi":"10.1007/s10549-025-07654-1","DOIUrl":"https://doi.org/10.1007/s10549-025-07654-1","url":null,"abstract":"<p><strong>Introduction: </strong>Outcome prediction research in early-onset breast cancer (EoBC) is limited. This study evaluated the predictive performance of NHS PREDICT v2.1 and developed two prediction models for 5-year and 10-year all-cause mortality in a cohort of EoBC patients in Alberta, Canada.</p><p><strong>Methods: </strong>Adults < 40 years diagnosed with invasive breast cancer in Alberta, Canada from 2004 to 2020 were included. Patient data were entered into PREDICT v2.1 and mortality estimates at 5 and 10 years were extracted. Two prediction models were developed for all-cause mortality: multivariable Cox regression with LASSO penalization (LASSO Cox) and random survival forests (RSF). Internal validation of the developed models was performed using nested tenfold cross-validation repeated 200 times. Model performance was assessed using receiver operator characteristic and calibration curves for mortality at 5 and 10 years.</p><p><strong>Results: </strong>In total, 1827 patients with EoBC were eligible for inclusion. At 5 years, PREDICT had an area under the curve of 0.78 (95%CI 0.74-0.82) and overestimated mortality by 2.4% (95%CI 0.70-4.33) in the overall cohort. No differences in observed and predicted mortality by PREDICT were observed at 10 years. The LASSO Cox model showed better discrimination at 5 and 10 years than the RSF model, but both had poor calibration and underestimated mortality.</p><p><strong>Conclusion: </strong>PREDICT v2.1 tended to overestimate 5-year mortality in those with > 30% predicted risks and 10-year mortality in those with > 50% predicted risks for EoBC in Alberta, Canada. We did not identify additional models that would be clinically useful by applying machine learning. More follow-up data and emerging systemic treatment variables are required to study outcome prediction in modern cohorts.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body composition as a potential biomarker of recurrence risk in patients with triple-negative breast cancer.","authors":"Jill B De Vis, Cong Wang, Kirsten V Nguyen, Lili Sun, Brigitte Jia, Alexander D Sherry, Mason N Alford-Holloway, Meridith L Balbach, Tatsuki Koyama, A Bapsi Chakravarthy, Marjan Rafat","doi":"10.1007/s10549-025-07675-w","DOIUrl":"10.1007/s10549-025-07675-w","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) patients are at increased risk for recurrence compared to other subtypes of breast cancer. Previous evidence showed that adiposity may contribute to worsened cancer control. Current measures of obesity, such as body-mass index (BMI), are poor surrogates of adiposity, while visceral-to-subcutaneous adiposity ratio (VSR), which can be measured from routine computed tomography (CT) imaging, is a direct adiposity measure. We hypothesized that VSR is a stronger predictor of recurrence compared with BMI in patients with TNBC.</p><p><strong>Materials and methods: </strong>This study includes 162 women with stage I-III TNBC who completed standard of care therapy. Measures of body composition, including VSR, visceral adiposity (VA), and subcutaneous adiposity (SA), were estimated using a semi-automated quantitative imaging tool on CT images of the abdomen at the level of L2-L3. Anthropometric measures included BMI and waist circumference and were obtained from CT images. Associations of adiposity measures and recurrence risk were assessed using Fine and Gray competing risk models with death as a competing risk and age at diagnosis and clinical disease stage as covariates.</p><p><strong>Results: </strong>During a median follow-up time of 7.1 years, 55 patients had recurrence. The median BMI at baseline was 30.2 [Quartiles: 26.3-35.2]. Body composition was not associated with overall or locoregional recurrence. VSR was significantly associated with an increased risk of distant recurrence, with a subdistribution hazard ratio of 4.25 (95% CI: 1.06-17.02), p = 0.041. By contrast, BMI was not associated with any recurrence risk.</p><p><strong>Conclusion: </strong>Consistent with our hypothesis, VSR was associated with a significant risk of distant recurrence and therefore may be a prognostic biomarker. Future directions include interventions targeting VSR reduction among patients with TNBC and VSR-directed therapy modulation.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of body mass index on breast cancer stage and breast cancer specific survival.","authors":"A Bellini, T H M Keegan, Q Li, A Jacinto, F B Maguire, V Lyo, C A M Sauder","doi":"10.1007/s10549-025-07678-7","DOIUrl":"https://doi.org/10.1007/s10549-025-07678-7","url":null,"abstract":"<p><strong>Purpose: </strong>Underweight women and those with obesity, defined as having a body mass index (BMI) ≥ 30 kg/m², diagnosed with breast cancer (BC) are known to have worse prognosis. Whether BMI impacts BC stage at diagnosis and BC specific survival (BCSS) is not understood. We aim to better understand the relationship between BMI with stage at BC diagnosis and BCSS.</p><p><strong>Methods: </strong>Women age ≥ 15 years old diagnosed with BC between 2014 and 2019 were identified from the California Cancer Registry. BMI at diagnosis was classified as underweight (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), obesity class 1-2 (30-39.9 kg/m²), and obesity class 3 (≥ 40 kg/m²). BC late stage of diagnosis was defined as American Joint Committee on Cancer stage 3 and 4. Multivariate logistic regression was performed to compare sociodemographic and clinical factors associated with late stage. Multivariable cox proportional hazards regression models assessed association of BMI and BCSS.</p><p><strong>Results: </strong>Of 159,248 patients: 2.2% were underweight, 34.6% normal weight, 30.5% overweight, 26.7% obesity class 1-2, and 6.0% obesity class 3. Compared to normal weight, patients who were underweight [Hazard Ratio (HR) 1.54, 95% Confidence Interval (CI) 1.51-1.57], obesity class 1-2 [HR 1.06, 1.05-1.07], and obesity class 3 [HR 1.14, 1.12-1.16] were more likely to be diagnosed with late-stage BC. In models stratified by age, patients ≥ 40 years who were underweight had worse BCSS, while patients ≥ 51 years with obesity class 1-2 had better BCSS.</p><p><strong>Conclusion: </strong>Patients with obesity class 1-2 were more likely to be diagnosed with a later stage, but had improved BCSS, supporting an \"obesity paradox\" in BC and suggesting that other measures are needed to better assess body composition, adipose distribution, and metabolic health of patients. Patients who were underweight had worse survival, suggesting this high-risk group may benefit from being assessed and treated for possible sarcopenia and malnourishment.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTEN inactivating mutations are associated with hormone receptor loss during breast cancer recurrence.","authors":"Haiying Zhan, Vijay Mariadas Antony, Haiming Tang, Janie Theriot, Yuanxin Liang, Pei Hui, Uma Krishnamurti, Michael P DiGiovanna","doi":"10.1007/s10549-025-07660-3","DOIUrl":"https://doi.org/10.1007/s10549-025-07660-3","url":null,"abstract":"<p><strong>Purpose: </strong>Hormone receptor (HR) status may be unstable during breast cancer (BC) progression, and changes occur in approximately 20-30% of BC patients at the time of recurrence. The biologic tumor switch from HR+ to HR- status is associated with worse clinical outcomes and warrants alternative management. We aimed to characterize clinical and pathologic features of a subset of ER+/HER2- breast cancer patients who converted to triple negative phenotype upon recurrence, and investigate the molecular alterations associated with HR loss during BC progression.</p><p><strong>Methods: </strong>We retrospectively identified 112 patients who had primary ER+/HER2- breast cancer and developed local or distant recurrence through our institutional database. Patients were divided into two cohorts based on receptor profile of recurrent tumor: discordant TNBC (n = 20) and concordant ER+/HER2- tumors. The following variables were collected: tumor histology, grade, pT, pN, ER, PR, HER2 expression in primary and recurrent tumors, molecular profiling, and adjuvant treatment history.</p><p><strong>Results: </strong>The average time for HR+ tumors to recur as TNBC was 148 months. The two cohorts showed similar clinicopathologic characteristics, including patient's age at diagnosis, tumor type, grade, stage, ER expression, and treatment history before tumor recurrence. PTEN inactivating mutations were more frequently identified in the discordant TNBC (6/20, 30%) compared to the concordant ER+/HER2- tumors (6/92, 5.5%) (p = 0.007).</p><p><strong>Conclusion: </strong>Increased signaling via the PI3K/AKT/PTEN pathway may be a mechanism for the transition to hormone independence in recurrent diseases.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}