Breast Cancer Research and Treatment最新文献

{"title":"Metastatic breast cancer through the Oncotype DX Breast Recurrence Score®: insights from a small cohort study.","authors":"Julie Anne L Gemmill, Patricia Thompson, Rebecca Batiste, Caterina Vacchi-Suzzi, Christina Preece, Jules Cohen, Lea Baer, Carolyn Mies, Michelle Turner, Christy A Russell, Alison Stopeck","doi":"10.1007/s10549-025-07736-0","DOIUrl":"https://doi.org/10.1007/s10549-025-07736-0","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the feasibility of obtaining a 21-gene Oncotype DX Breast Recurrence Score® (RS) result from metastatic biopsies in newly diagnosed hormone receptor positive, HER2- metastatic breast cancer patients and correlate RS results with matched primary samples.</p><p><strong>Methods: </strong>Retrospective analysis of metastatic biopsies from HR+, HER2- breast cancer patients. Slides were sent to Genomic Health, Inc. for RNA isolation and RS determination. Success rates were evaluated across metastatic sites, and RS results were compared between matched primary and metastatic samples.</p><p><strong>Results: </strong>RS result was obtained in 46% of metastatic biopsies (bone: 18; liver: 5; lung: 1; ovary: 1; skin: 1). Failures were primarily due to insufficient (18) or poor-quality RNA (8). Mean RS for metastatic sites was 33 (range 1-66). None gained HER2 expression by RT-PCR. In 19 paired samples, mean RS was 20 (range 7-35) for primary and 35 (range 1-66) for metastatic sites, showing no predictive correlation. Estrogen receptor (ER) was conserved in 90%, while progesterone receptor (PR) was lost in 37%. In six de novo cases, metastatic RS result was consistently higher than primary RS (mean 36 vs. 24). ER positivity and HER2-negativity showed 100% concordance; PR expression had 67% concordance.</p><p><strong>Conclusion: </strong>RS generation from metastatic biopsy samples was feasible in 46% of cases. Results revealed higher RS in metastatic disease, frequent PR loss, and poor correlation with primary tumors. Adequate tissue sampling is essential for improving RNA quality and test success. Further research into RS result relevance in metastatic treatment decisions is warranted.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172836","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":"Subtype-specific dysregulation of biogenic amine-related genes and miRNAs in breast cancer: identification of DRD2, HRH2, and HRH4 as potential therapeutic targets in TNBC and HER2+ subtypes.","authors":"Agata Sirek, Tomasz Sirek, Robert Nowakowski, Przemysław Borawski, Piotr Ossowski, Katarzyna Mitka-Krysiak, Nikola Zmarzły, Kacper Boroń, Michał Chalcarz, Bernadeta Kuraszewska, Mariola Szulik, Dariusz Boroń, Beniamin Oskar Grabarek","doi":"10.1007/s10549-025-07732-4","DOIUrl":"https://doi.org/10.1007/s10549-025-07732-4","url":null,"abstract":"<p><strong>Purpose: </strong>Biogenic amines (BAs) are known to influence tumorigenesis, yet their precise role in breast cancer remains unclear. This study aimed to investigate the expression patterns of BA-related genes, proteins, and their regulatory miRNAs across different breast cancer subtypes to identify potential biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>A cohort of 501 breast cancer patients was classified into luminal A (n = 130), luminal B HER2- (n = 100), luminal B HER2+ (n = 96), non-luminal HER2+ (n = 36), and triple-negative breast cancer (TNBC; n = 43). Gene expression was assessed via microarray analysis and validated using RT-qPCR. Protein levels were quantified using ELISA, while miRNA profiling was conducted to identify post-transcriptional regulatory interactions. Statistical significance was determined using ANOVA and Tukey's post-hoc test (p < 0.05).</p><p><strong>Results: </strong>Histamine-related genes (HRH1-HRH4) were upregulated across all subtypes, with HRH2 and HRH4 most elevated in TNBC (FC = 7.18, p < 0.01). DRD2 showed widespread upregulation (FC = 15.98, p < 0.001), whereas DRD5 was markedly downregulated, especially in non-luminal HER2+ tumors (FC =  - 13.01, p < 0.01). miRNA analysis revealed downregulation of hsa-miR-30b-3p and hsa-miR-372-5p in TNBC and HER2+ subtypes, correlating with HRH2 and HRH4 overexpression (p < 0.05). EGR1 and ICAM1 exhibited strong subtype-specific expression, with ICAM1 significantly upregulated in TNBC (FC = 25.76, p < 0.001).</p><p><strong>Conclusion: </strong>Subtype-specific dysregulation of BA-related genes and miRNAs suggests their involvement in tumor progression, immune modulation, and metabolic regulation. The findings highlight potential therapeutic targets, particularly in TNBC and HER2+ subtypes.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156749","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":"Integrating SENOMAC and AMAROS: a call for de-escalation.","authors":"Raquel Diaz, Rebecca Allievi, Piero Fregatti","doi":"10.1007/s10549-025-07743-1","DOIUrl":"https://doi.org/10.1007/s10549-025-07743-1","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149424","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":"Timely germline BRCA testing after invasive breast cancer promotes contralateral risk-reducing mastectomy and improves survival: an observational retrospective study.","authors":"Aleksandar M Kostov, Maj-Britt Jensen, Bent Ejlertsen, Mads Thomassen, Maria Rossing, Inge S Pedersen, Annabeth H Petersen, Lise Lotte Christensen, Karin A W Wadt, Luis C Berrocal-Almanza, Miguel Miranda, Anne-Vibeke Lænkholm","doi":"10.1007/s10549-025-07726-2","DOIUrl":"https://doi.org/10.1007/s10549-025-07726-2","url":null,"abstract":"<p><strong>Purpose: </strong>To report the rates of risk-reducing surgery (RRS) following germline testing for BRCA1/2 (likely) pathogenic variants (BRCApv) and to assess the impact of RRS and BRCA status on survival after surgical treatment for unilateral breast cancer (BC).</p><p><strong>Methods: </strong>We identified 7145 women with BC (2000-2017), a BRCA test and median follow-up of 10.8 years from the Danish Breast Cancer Cooperative Group's clinical database. Distant recurrence-free (DRFS) and overall survival (OS) according to BRCA status were evaluated using the Kaplan-Meier method. Hazard ratios (HR) for BRCApv vs. BRCA wild-type, contralateral risk-reducing mastectomy (CRRM), and risk-reducing bilateral salpingo-oophorectomy (RRBSO), including interaction tests, were estimated using multivariable Cox models.</p><p><strong>Results: </strong>Among BRCA1pv carriers (n = 403), CRRM rates were higher than in BRCA2pv (n = 317) (66% vs. 52%, p < 0.001) and more likely to receive timely testing, i.e., within 6 months of BC diagnosis (75% vs. 52%, p = 0.004). Regarding RRBSO rates, no differences were observed. CRRM was associated with significantly improved DRFS (HR = 0.63, 95% CI 0.51-0.78) and OS (HR = 0.64, 95% CI 0.51-0.82), independently of BRCA status and age. RRBSO was associated with improved OS only in BRCApv carriers, specifically, those aged ≥ 50 years (HR = 0.44, 95% CI 0.26-0.75). BRCApv (irrespective of affected gene) was associated with worse DRFS (HR = 1.31, 95% CI 1.06-1.63); however, this was only evident after 2 years of follow-up (HR = 1.53, 95% CI 1.22-1.93). BRCApv was not significantly associated with worse OS (HR = 1.25, 95%CI 0.98-1.58).</p><p><strong>Conclusion: </strong>Timely germline testing at BC diagnosis might increase CRRM rates in BRCApv carriers, thereby improving survival.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126685","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":"Invasive lobular breast carcinoma variants; clinicopathological features and patient outcomes.","authors":"Aysegul Aktas, Meryem Gunay Gurleyik, Dogukan Akkus, Zekeriya Ucur, Fugen Aker","doi":"10.1007/s10549-025-07729-z","DOIUrl":"https://doi.org/10.1007/s10549-025-07729-z","url":null,"abstract":"<p><strong>Introduction: </strong>An understanding of the differences among the invasive lobular breast carcinoma (ILC) variants is crucial for risk stratification, and tailored treatment planning. This article compares variants of ILC according to their clinical outcomes and histopathological features.</p><p><strong>Patients and methods: </strong>Patients diagnosed with ILC between January 2010 and August 2021 were retrospectively evaluated. Patients were divided into three groups; 1: classic ILC (cILC); 2: pleomorphic lobular carcinoma (PLC); 3: mixed ILC. Mixed ILC was divided into three subgroups: 3a, cILC + PLC; 3b, cILC + mixed; 3c, PLC + mixed.</p><p><strong>Results: </strong>A total of 254 patients were included in the study. Median overall survival (OS) was 48 months, and median disease-free survival (DFS) was 46 months. Locoregional recurrence (LRR) occurred in 15 (5.9%) of the patients, and distant metastasis (DM) developed in 23 (9.1%). Death occurred in 16 (6.3%) patients. There was no significant difference in LRR rate among groups. When considering five groups (Groups 1, 2, 3a, 3b, and 3c), the median OS was 62.5, 52.0, 50.8, 56.7, and 41.5 months, respectively, while the median DFS was 60.3, 46.6, 46.7, 54.5, and 39.6 months, respectively. Notably, the PLC + mixed group without a classic variant (Group 3c) exhibited even worse outcomes than pure PLC.</p><p><strong>Conclusions: </strong>In this study, pure cILC exhibited the best prognostic features among the ILC variants. Furthermore, we observed a higher mastectomy rate in patients with pleomorphic variants. Surgical management of ILC remains controversial. Moreover, comprehensive randomized controlled trials are essential to establish standardized treatment protocols for ILC patients.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109571","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":"Social determinants of cardiovascular disease in women with and without breast cancer.","authors":"Elena Wadden, Vidhushei Yogeswaran, Roberta M Ray, Alexi Vasbinder, Aladdin H Shadyab, Qian Xiao, Phyllis A Richey, Nazmus Saquib, Yangbo Sun, Su Yon Jung, Margaret S Pichardo, JoAnn E Manson, Garnet Anderson, Michael Simon, Marcia L Stefanick, Kerryn Reding, Ana Barac, Richard K Cheng","doi":"10.1007/s10549-025-07731-5","DOIUrl":"https://doi.org/10.1007/s10549-025-07731-5","url":null,"abstract":"<p><strong>Purpose: </strong>Social determinants of health (SDOH) may impact cardiovascular (CV) risk in women with and without breast cancer (BC).</p><p><strong>Methods: </strong>In 153,401 participants without prevalent CV disease from the Women's Health initiative (WHI), we assessed key SDOH factors: geographic region, rurality, insurance status, and household income. Multivariable Cox proportional hazards models were used to assess associations between SDOH factors and a composite CV outcome, which included incident myocardial infarction, incident stroke, hospitalization for heart failure, or CV death.</p><p><strong>Results: </strong>In the final cohort, 10,954 (mean ± standard deviation [SD] age 62 ± 7 years) women developed BC, and 142,144 (mean age 63 ± 7 years) women remained free of BC. During a median follow-up time of 13 years, 18,148 women experienced the composite CV outcome. Rurality, low household income, and non-private insurance were associated with an increased risk of the composite CV outcome and CV death, both in women with and without BC.</p><p><strong>Conclusions: </strong>SDOH factors are associated with an increased risk of CV events among women, irrespective of BC status. These associations highlight the importance of socioeconomic factors across cardiovascular health outcomes.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109603","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":"Management of ipsilateral breast tumor recurrence after prior breast conservation therapy.","authors":"Jacob M Jasper, Halley Vora, Olga Kantor, Monica McGrath, Jennifer R Bellon, Elizabeth A Mittendorf, Tari A King","doi":"10.1007/s10549-025-07730-6","DOIUrl":"https://doi.org/10.1007/s10549-025-07730-6","url":null,"abstract":"<p><strong>Purpose: </strong>Mastectomy is traditionally recommended for local recurrence after breast conservation therapy (BCT), the combination of lumpectomy followed by whole-breast radiotherapy. Recent studies suggest that repeat BCT (lumpectomy and re-irradiation) may be feasible for select patients. We sought to evaluate the clinical characteristics, management strategies, and outcomes of patients treated for ipsilateral breast tumor recurrence (IBTR) after initial BCT and assess the impact of a newly adopted multidisciplinary algorithm for repeat BCT (lumpectomy and re-irradiation).</p><p><strong>Methods: </strong>We identified patients with stage 0-III breast cancer treated with initial BCT who underwent surgery for IBTR between January 2016 and May 2023. Patient, tumor, and treatment characteristics were analyzed, and outcomes were compared before and after the adoption of the repeat BCT algorithm.</p><p><strong>Results: </strong>Among 546 patients treated for IBTR, 48% were eligible for repeat BCT. After criteria adoption, mastectomy rates decreased by 16%. The proportion of eligible patients undergoing lumpectomy alone (BCS) for IBTR increased by 9% while only a modest increase in lumpectomy and re-irradiation (repeat BCT) was observed (7%). Rates of BCS for IBTR were higher than repeat BCT among older patients. Clinical outcomes were comparable between patients treated with BCS, BCT, or mastectomy.</p><p><strong>Conclusion: </strong>Repeat BCT (lumpectomy and re-irradiation) is a viable option for select patients with IBTR, offering comparable outcomes to mastectomy. The adoption of standardized criteria for repeat BCT has increased its use, highlighting the importance of multidisciplinary approaches in treatment planning.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109586","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":"Effect of chemotherapy timing in triple-negative breast cancer: a real-world evidence study.","authors":"Noiver Graciano, Lucelly López, Carlos A Rodriguez, Katherine Montoya, Diego M González, Luis Rodolfo Gómez, Maycos L Zapata, Javier Cortés","doi":"10.1007/s10549-025-07716-4","DOIUrl":"https://doi.org/10.1007/s10549-025-07716-4","url":null,"abstract":"<p><strong>Purpose: </strong>Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous malignancy with poor prognosis. The optimal timing of chemotherapy-neoadjuvant (NACT) versus adjuvant (ACT)-remains controversial. This study assessed real-world outcomes in non-metastatic TNBC patients according to chemotherapy timing.</p><p><strong>Methods: </strong>This retrospective study (2008-2023) evaluated the impact of chemotherapy timing on overall survival (OS) and event-free survival (EFS) in a cohort of 711 patients. Propensity score (PS) matching with preoperative variables was used to adjust for baseline imbalances, and Cox regression models were applied to account for treatment-related variables.</p><p><strong>Results: </strong>NACT was administered to 525 patients (73.8%), with a 37.3% pathological complete response (pCR) rate. PS matching yielded 177 patient pairs; tumor stage, age and histologic grade remained unbalanced. In the unadjusted analysis, NACT was associated with worse OS (HR 1.56, 95% CI1.08-2.25, p = 0.018). However, multivariate analysis adjusting for unmatched and postoperative variables showed a potential benefit of NACT for OS (HR 0.53, 95% CI 0.07-4.13, p = 0.545) and EFS (HR 0.94, 95% CI 0.21-4.17, p = 0.932). Tumor stage acted as an effect modifier, and stratified analyses revealed that NACT was superior to ACT in patients with advanced-stage disease who achieved pCR (HR 0.22, 95% CI 0.07-0.7, p < 0.010).</p><p><strong>Conclusions: </strong>In our TNBC cohort, chemotherapy timing significantly influenced OS and EFS, particularly in relation to initial tumor stage and pCR status. NACT was more beneficial than ACT in patients with advanced disease who achieve pCR, underscoring its role in both prognostic stratification and therapeutic decision-making.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118793","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":"Omission of multimodal therapy in older adults with high-risk breast cancer.","authors":"Eliza H Lorentzen, Yu-Jen Chen, Annabelle L Jones, Olga Kantor, Tari A King, Elizabeth A Mittendorf, Christina A Minami","doi":"10.1007/s10549-025-07728-0","DOIUrl":"https://doi.org/10.1007/s10549-025-07728-0","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment guidelines recommend multimodal therapy for non-metastatic high-risk breast cancer in older adults. However, older patients may be less likely to receive this due to varying abilities to withstand intensive therapy. We aimed to quantify the incidence of, factors associated with, and reasons behind omission of multimodal therapy in older high-risk breast cancer patients.</p><p><strong>Methods: </strong>Women ≥ 70 years diagnosed with stage 2-3 HR-/HER2+ or triple-negative breast cancer were identified in the National Cancer Database, 2010-2020. Multimodal therapy was defined as surgery and systemic therapy; omission of multimodal therapy was defined as patients who did not receive one or both therapies. Chi-square tests were used to assess differences by therapy intensity. Multivariable logistic regression models adjusting for patient and disease-level characteristics were performed to determine the factors associated with therapy omission.</p><p><strong>Results: </strong>Of 22,644 patients, 63.4% were ≤ 80 years old. Overall, 59.7% received multimodal therapy, 35.3% received either surgery or systemic therapy, and 5.0% received no therapy. Factors significantly associated with increased likelihood of multimodal therapy omission included increased age, Black race, Medicaid or uninsured status, and higher Charlson Comorbidity Index scores. The most common reason for omission was that it was \"not part of planned treatment,\" (59.2% for omission of surgery, 52.4% for omission of systemic therapy), with patient refusal (17.4% for omission of surgery, 28.3% for omission of systemic therapy) being second most common.</p><p><strong>Conclusions: </strong>While most older patients received multimodal therapy, demographic and socioeconomic factors associated with treatment omission suggest that some vulnerable women with high-risk disease may be undertreated.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109590","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":"Predicting the likelihood of carrying BRCA1 or BRCA2 pathogenic variants in high-risk Pakistani breast cancer patients.","authors":"Shumaila Arif, Noor Muhammad, Boon Hong Ang, Humaira Naeemi, Waqas Sami, Weang Kee Ho, Ute Hamann, Muhammad Usman Rashid","doi":"10.1007/s10549-025-07724-4","DOIUrl":"https://doi.org/10.1007/s10549-025-07724-4","url":null,"abstract":"<p><strong>Purpose: </strong>Pathogenic variants (PVs) in BRCA1/2 increase the lifetime risk of breast cancer (BC). Predictive algorithms for BRCA1/2 PVs, primarily developed for Caucasian BC patients, often underestimate carrier probability in Asian populations. The recently developed Asian Risk Calculator (ARiCa) aims to predict BRCA1/2 PV likelihood in Malaysian/Singaporean BC patients. This study investigates the ARiCa's performance in Pakistani female BC patients.</p><p><strong>Methods: </strong>A cohort of 627 high-risk Pakistani female BC patients was evaluated. Using ARiCa, the likelihood of being a BRCA1/2 carrier was estimated based on factors such as age at diagnosis, ethnicity, bilateral BC status, tumor histopathological features, and family history of BC or ovarian cancer. The tool's discriminative ability was evaluated using the area under the curve (AUC).</p><p><strong>Results: </strong>Of the participants, 133 (21.2%) were BRCA1 carriers, 25 (4.0%) were BRCA2 carriers, and 469 (74.8%) were non-carriers. The mean age at BC diagnosis was 34.3 years (range 19-73). Overall, ARiCa showed well calibration for predicting BRCA1/2 (HL 12.11, P = 0.147), BRCA1 (HL 14.17, P = 0.078), and BRCA2 carriers (HL 9.01, P = 0.342). The tool showed acceptable discrimination for BRCA1/2 (AUC 0.77, 95% CI 0.72-0.81) and BRCA1 carriers (AUC 0.80, 95% CI 0.75-0.84), but lower discrimination for BRCA2 carriers (AUC 0.51, 95% CI 0.39-0.64). At a 21% threshold, ARiCa would recommend BRCA1/2 screening for 43% of patients, with sensitivity and specificity at 73% and 68%, respectively.</p><p><strong>Conclusion: </strong>The ARiCa tool demonstrates strong predictive performance for BRCA1/2 carriers, specifically for BRCA1 carriers in Pakistani BC patients, suggesting its potential clinical utility.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109596","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}