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Time trends, uptake, and oncological effects of risk-reducing surgeries in 3067 Danish BRCA1/2 carriers: a population-based study with matched controls. 3067名丹麦BRCA1/2携带者降低风险手术的时间趋势、摄取和肿瘤效应:一项基于人群的匹配对照研究
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-20 DOI: 10.1007/s10549-025-07821-4
Cecilie Balslev Willert, Lene Mellemkjær, Anders Tolver, Anne-Marie Axø Gerdes, Susanne Rosthøj, Karin Wadt, Niels Kroman, Pernille Envold Bidstrup, Lisbet Rosenkrantz Hölmich
{"title":"Time trends, uptake, and oncological effects of risk-reducing surgeries in 3067 Danish BRCA1/2 carriers: a population-based study with matched controls.","authors":"Cecilie Balslev Willert, Lene Mellemkjær, Anders Tolver, Anne-Marie Axø Gerdes, Susanne Rosthøj, Karin Wadt, Niels Kroman, Pernille Envold Bidstrup, Lisbet Rosenkrantz Hölmich","doi":"10.1007/s10549-025-07821-4","DOIUrl":"https://doi.org/10.1007/s10549-025-07821-4","url":null,"abstract":"<p><strong>Purpose: </strong>Knowledge of the uptake and breast and ovarian cancer-preventive and survival effects of bilateral risk-reducing mastectomy (BRRM) and salpingo-oophorectomy (RR-BSO) in female BRCA1/2 carriers is essential for optimized decision-making. This study aimed to examine time trends in the number of registered unaffected BRCA1/2 carriers, BRRM and RR-BSO uptake, and oncological effects of risk-reducing surgeries in a nationwide Danish cohort with matched controls.</p><p><strong>Methods: </strong>We included 3067 female BRCA1/2 carriers registered in the Hereditary Breast and Ovarian Cancer Registry and 30,652 age-matched controls between 2000 and 2022. Data were retrieved from national health registries. Uptake and oncological effects of risk-reducing surgeries were assessed using cumulative incidences and Cox proportional hazards models with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Annual numbers of registered unaffected BRCA1/2 carriers, BRRM, and RR-BSO increased over time. BRRM and RR-BSO uptake 10 years after genetic test varied with the age at genetic test and parity. BRRM reduced the hazard rate of breast cancer by 94% [hazard ratio (HR) 0.06, CI 0.01-0.25]. The same pattern was not found for RR-BSO (HR = 1.31, CI 0.90-1.91). Compared to controls, BRCA1/2 carriers had an increased hazard rate for breast cancer before BRRM (HR 7.49, CI 5.81-9.42).</p><p><strong>Conclusion: </strong>BRRM's large protective effect against breast cancer in BRCA1/2 carriers was confirmed, in contrast to that of RR-BSO. There were tendencies toward a reduction in overall mortality rates after BRRM, and compared with controls, we saw tendencies toward higher mortality rates before BRRM.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091113","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}
引用次数: 0
Pathological complete response and survival outcomes in single hormone receptor-positive/HER2-negative breast cancer after neoadjuvant chemotherapy and its intrinsic biological features and immune landscape. 单激素受体阳性/ her2阴性乳腺癌新辅助化疗后的病理完全缓解和生存结局及其内在生物学特征和免疫景观
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-17 DOI: 10.1007/s10549-025-07822-3
Lei Ji, Xi Chen, Hongwei Lyu, Ge Song, Min Xiao, Qing Li, Jiayu Wang, Ying Fan, Yang Luo, Qiao Li, Shanshan Chen, Fei Ma, Binghe Xu, Pin Zhang
{"title":"Pathological complete response and survival outcomes in single hormone receptor-positive/HER2-negative breast cancer after neoadjuvant chemotherapy and its intrinsic biological features and immune landscape.","authors":"Lei Ji, Xi Chen, Hongwei Lyu, Ge Song, Min Xiao, Qing Li, Jiayu Wang, Ying Fan, Yang Luo, Qiao Li, Shanshan Chen, Fei Ma, Binghe Xu, Pin Zhang","doi":"10.1007/s10549-025-07822-3","DOIUrl":"https://doi.org/10.1007/s10549-025-07822-3","url":null,"abstract":"<p><strong>Background: </strong>Previous studies often combined double hormone receptor-positive (dHR +) and single HR-positive (sHR +) tumors, thus not accounting for the distinct characteristics of sHR + , particularly in the neoadjuvant setting. Moreover, adding immunotherapy to cytotoxic chemotherapy has shown encouraging efficacy in certain HR-positive early breast cancers. This study sought to assess pathological complete response (pCR) and survival outcomes in sHR + /HER2- breast cancer after neoadjuvant chemotherapy, while also investigating its specific biological traits and immune profile.</p><p><strong>Methods: </strong>Clinical data were sourced from the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS, n = 1049), and the Surveillance, Epidemiology, and End Results (SEER, n = 21,092) database to examine neoadjuvant chemosensitivity and survival outcomes. Additionally, clinicopathological and subtype data from CHCAMS, SEER, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1052), and Fudan University Shanghai Cancer Center (FUSCC, n = 570) were analyzed to identify biological features that correlate with pCR rates and prognosis in sHR + /HER2- breast cancer. Further genomic and transcriptomic data from METABRIC, The Cancer Genome Atlas (TCGA, n = 741), and MSK-IMPCAT (n = 1535) were reviewed to uncover their potential links with endocrine and immunotherapy responses.</p><p><strong>Results: </strong>In comparison to dHR + (ER + and PR +)/HER2- breast cancer, sHR + (ER + /PR- or ER-/PR +)/HER2- breast cancer displayed a higher pCR rate (20.2% vs. 3.2%, P < 0.001), but considerably worse survival (hazard ratio, 2.97; 95% confidence interval, 1.62-5.43, P < 0.001) within the CHCAMS neoadjuvant cohort. Clinically, sHR + /HER2- tumors were associated with higher histological grades and proliferation rates compared to dHR + /HER2- tumors, along with a greater rate of HR-low positivity (50.9% vs. 3.0%, P < 0.001) in primary tumors and a tendency to transition to triple-negative tumors in residual disease (42.7% vs. 1.8%, P < 0.001). Furthermore, sHR + /HER2- breast cancers demonstrated lower endocrine sensitivity scores, with about 20% classified as PAM50-defined basal-like subtype. Immunologically, sHR + /HER2- tumors had elevated tumor mutation burden (TMB), higher expression of immune checkpoint genes (e.g., PD-1, PD-L1, CTLA4), and greater infiltration by tumor-infiltrating lymphocytes (TILs), particularly CD8 + T cells, than dHR + /HER2- tumors.</p><p><strong>Conclusion: </strong>Compared to dHR + /HER2- breast cancer, sHR + /HER2- cases showed a relative sensitivity to neoadjuvant chemotherapy but poorer prognosis. The immune-activated phenotype of sHR + /HER2- breast cancer indicates that it may benefit from immunotherapy approaches, but these findings warrant validation in prospective studies.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079848","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}
引用次数: 0
Breast surgical site infections in patients undergoing lumpectomy with and without closure of defect. 有或没有闭合缺陷的乳房肿瘤切除术患者的乳房手术部位感染。
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-13 DOI: 10.1007/s10549-025-07819-y
Emily Palmquist, Risa Kiernan, Varadan Sevilimedu, Tiana Le, Monica Morrow, Mahmoud El-Tamer
{"title":"Breast surgical site infections in patients undergoing lumpectomy with and without closure of defect.","authors":"Emily Palmquist, Risa Kiernan, Varadan Sevilimedu, Tiana Le, Monica Morrow, Mahmoud El-Tamer","doi":"10.1007/s10549-025-07819-y","DOIUrl":"https://doi.org/10.1007/s10549-025-07819-y","url":null,"abstract":"<p><strong>Purpose: </strong>Postoperative infection rates in the United States following breast cancer surgery, including mastectomy with or without reconstruction, range from 2-26%. Management of post-lumpectomy defects may involve simple skin closure or oncoplastic closure; however, the effect of defect repair on postoperative infection rates has not been well documented. Here we determine how oncoplastic closure of partial mastectomy defects affects postoperative infection rates and antibiotic use.</p><p><strong>Methods: </strong>In this retrospective single-institution study, patients undergoing lumpectomy with and without oncoplastic closure of defect were included between 2018-2020. Clinicopathologic/treatment data were collected from medical records. Patients receiving antibiotics on postoperative days 5-30 were reviewed to confirm wound infection. Associations between demographic and clinicopathologic factors and postoperative infections were analyzed.</p><p><strong>Results: </strong>3937 patients met eligibility criteria; 2273 (58%) had oncoplastic closure. The overall postoperative wound infection rate (includes cellulitis) was 8.4% (332), and true surgical site infection, as defined by the CDC (excludes cellulitis), was seen in 70 (1.8%) patients. On univariate analysis, age ≥ 60 years, diabetes, hypertension, and BMI ≥ 30 were associated with increased breast infection. Oncoplastic closure was protective against postoperative breast infections (odds ratio [OR]0.70, p = 0.040). On multivariable analysis oncoplastic closure had marginally decreased breast infection rates (OR 0.71, p = 0.053); however, this was not significant. BMI ≥ 30 was the only risk factor that remained a significant predictor of increased breast infection rates (OR1.63, p = 0.021).</p><p><strong>Conclusions: </strong>Oncoplastic closure of lumpectomy defects had marginally significant lower rates of postoperative breast infections. As oncoplastic techniques are increasingly adopted in breast-conserving surgery, it is important to further study the protective nature of lumpectomy defect closure to reduce postoperative infection rates.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051851","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}
引用次数: 0
Evaluation of efficacy and safety of sequential antibody drug conjugates (ADCs) in human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. 序贯抗体药物偶联物(adc)治疗人表皮生长因子2 (HER2)阴性转移性乳腺癌的疗效和安全性评价
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-11 DOI: 10.1007/s10549-025-07818-z
Sara Nezirevic, Carey Anders, Susan Dent, Rani Bansal, Lexie Zidanyue Yang, Alaattin Erkanli, Heather Moore
{"title":"Evaluation of efficacy and safety of sequential antibody drug conjugates (ADCs) in human epidermal growth factor 2 (HER2)-negative metastatic breast cancer.","authors":"Sara Nezirevic, Carey Anders, Susan Dent, Rani Bansal, Lexie Zidanyue Yang, Alaattin Erkanli, Heather Moore","doi":"10.1007/s10549-025-07818-z","DOIUrl":"https://doi.org/10.1007/s10549-025-07818-z","url":null,"abstract":"<p><strong>Purpose: </strong>Limited data is available assessing sequencing of antibody drug conjugates (ADCs) in patients with hormone receptor-positive (HR +), human epidermal growth factor 2 (HER2)-negative, HER2-low, and triple-negative metastatic breast cancer (MBC), including patients with brain metastases (BrM) or leptomeningeal disease (LMD). This study assesses the efficacy and safety of sequential sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) in MBC and impact on chemotherapy (CTX).</p><p><strong>Methods: </strong>This is a single-center, retrospective, cohort study in adult patients with HR + , HER2-negative, or low MBC who received T-DXd and/or SG.</p><p><strong>Results: </strong>A total of 112 patients were divided into three cohorts: ADCs given sequentially (cohort A), ADC then CTX (cohort B), or CTX between ADCs (cohort C). The median progression-free survival (mPFS) in cohort A was 4.5 months for SG before T-DXd and 3.1 months for T-DXd before SG. In cohort B, mPFS was 3.1 months for CTX following T-DXd. For CTX following SG, mPFS for CTX was 2.5 months. In patients who received both ADCs, PFS was 2.1 months. In cohort C, mPFS for SG following T-DXd and CTX was 2.1 months and 3.3 months for T-DXd following SG and CTX. The mPFS for ADC1 was longer than ADC2 (5.5 months SG, 3.4 months T-DXd). Those with BrM and/or LMD demonstrated stable disease.</p><p><strong>Conclusion: </strong>Sequential administration of ADCs results in a shorter PFS. CTX efficacy is impacted by prior ADC administration. Outcomes for patients with BrM and LMD do not differ for those without recurrence to the brain.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032741","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}
引用次数: 0
Prescription and self-reported use of endocrine therapy among black hormone receptor-positive breast cancer survivors in the Detroit Research on Cancer Survivors cohort. 底特律癌症幸存者研究队列中黑色激素受体阳性乳腺癌幸存者的处方和自我报告使用内分泌治疗
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-09 DOI: 10.1007/s10549-025-07816-1
Abigail M Fielder, Seongho Kim, Julie J Ruterbusch, Cydnie Martin, Anna Gottschlich, Ann G Schwartz, Jennifer L Beebe-Dimmer, Hadeel Assad, Lauren Hamel, Kristen S Purrington
{"title":"Prescription and self-reported use of endocrine therapy among black hormone receptor-positive breast cancer survivors in the Detroit Research on Cancer Survivors cohort.","authors":"Abigail M Fielder, Seongho Kim, Julie J Ruterbusch, Cydnie Martin, Anna Gottschlich, Ann G Schwartz, Jennifer L Beebe-Dimmer, Hadeel Assad, Lauren Hamel, Kristen S Purrington","doi":"10.1007/s10549-025-07816-1","DOIUrl":"https://doi.org/10.1007/s10549-025-07816-1","url":null,"abstract":"<p><strong>Purpose: </strong>Black women with hormone receptor-positive (HR +) breast cancer are twice as likely as White women to have weakly HR + tumors (1-10% positive cells). Patients with weakly HR + tumors are less frequently prescribed ET and have 60% higher mortality than strongly HR + tumors (> 10% positive cells). We evaluated factors associated with ET prescription and self-reported use among Black women with HR + breast cancer.</p><p><strong>Methods: </strong>Among 922 Detroit ROCS participants, we evaluated associations between demographics, socioeconomic status, and health, tumor, oncologist, and hospital characteristics and ET prescription intent and self-reported ET use. Logistic mixed-effects regression was used to account for oncologist and hospital group effects.</p><p><strong>Results: </strong>Oncologists intended to prescribe ET to 83.4% of participants (n = 769), of which 54.4% (n = 502) reported use. In multivariable models, participants with weakly HR + tumors were 90% less likely to be prescribed ET (OR = 0.10, p < 0.0001). Other significant characteristics of ET prescription included a BMI of 25-29.9 kg/m<sup>2</sup> (OR = 0.45, p = 0.0085), HR positivity > 90% vs. 11-90% (OR = 0.37, p = 0.00045), unknown HR percentage (OR = 0.12, p < 0.0001), OncotypeDx testing (OR = 2.65, p < 0.0001), and receiving radiation (OR = 2.20, p = 0.00016). Self-reported ET use was lower among those with lower health literacy (OR = 0.017, p < 0.001), weak HR positivity (OR = 0.46, p = 0.0053), unknown HR percentage (OR = 0.074, p = 0.034), and older age at diagnosis (OR = 0.88, p = 0.002). Increased ET use was associated with an income between $60,000-$79,900 vs. < $20,000 (OR = 1.54, p = 0.035), higher comorbidity count (OR = 1.09, p = 0.0054), distant stage (OR = 2.03, p = 0.029), and surgery (OR = 2.35, p = 0.001).</p><p><strong>Conclusion: </strong>Identifying multilevel factors related to ET use may inform strategies to improve ET uptake and survival among Black women with HR + breast cancer.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022912","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}
引用次数: 0
Correction to: 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. 乳腺癌中生物胺相关基因和mirna亚型特异性失调:鉴定DRD2、HRH2和HRH4作为TNBC和HER2 +亚型的潜在治疗靶点。
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-05 DOI: 10.1007/s10549-025-07807-2
Agata Sirek, Tomasz Sirek, Robert Nowakowski, Przemysław Borawski, Piotr Ossowski, Elżbieta Mitka-Krysiak, Nikola Zmarzły, Kacper Boroń, Michał Chalcarz, Bernadeta Kuraszewska, Mariola Szulik, Dariusz Boroń, Beniamin Oskar Grabarek
{"title":"Correction to: 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, Elżbieta Mitka-Krysiak, Nikola Zmarzły, Kacper Boroń, Michał Chalcarz, Bernadeta Kuraszewska, Mariola Szulik, Dariusz Boroń, Beniamin Oskar Grabarek","doi":"10.1007/s10549-025-07807-2","DOIUrl":"https://doi.org/10.1007/s10549-025-07807-2","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999575","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}
引用次数: 0
Immediate and ipsilateral recurrence rates and treatment recommendations for patients with pleomorphic and florid lobular carcinoma in situ. 多形性和花状小叶原位癌患者的即刻和同侧复发率及治疗建议。
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-01 Epub Date: 2025-07-10 DOI: 10.1007/s10549-025-07771-x
Lavinia P Middleton, George H Perkins, Gary J Whitman, Jason A Mouabbi, Therese B Bevers, Min Yi, Kelly K Hunt
{"title":"Immediate and ipsilateral recurrence rates and treatment recommendations for patients with pleomorphic and florid lobular carcinoma in situ.","authors":"Lavinia P Middleton, George H Perkins, Gary J Whitman, Jason A Mouabbi, Therese B Bevers, Min Yi, Kelly K Hunt","doi":"10.1007/s10549-025-07771-x","DOIUrl":"10.1007/s10549-025-07771-x","url":null,"abstract":"<p><strong>Background: </strong>Follow-up data are limited regarding the natural history of patients diagnosed with pleomorphic lobular carcinoma in situ (PLCIS) and florid lobular carcinoma in situ (FLCIS).</p><p><strong>Methods: </strong>This retrospective study identified patients with PLCIS and FLCIS. Clinicopathologic findings were evaluated. Patients with concurrently diagnosed ipsilateral breast cancer or ductal carcinoma in situ were excluded. The immediate and delayed risk of developing breast cancer was calculated.</p><p><strong>Results: </strong>All 45 patients were female, and the median age was 61 years. The most common imaging finding was suspicious calcifications on screening mammogram in 84.4%. The histology was PLCIS in 75.6% of cases (34/45), FLCIS in 11.1% (5/45), and a combination of variant types in 13% (6/45). Forty-four patients underwent surgery to include wide local excision in 84% (37/44) and mastectomy in 15.9% (7/44). One patient (2.3%) had concurrent DCIS on excision and ten patients (22.7%) had diagnoses upgraded to invasive carcinoma on excision, the majority being T1a (70%) and the remainder T1b (30%). These aforementioned patients were excluded from further outcome analysis. There were four patients (8.8%) with PLCIS who developed ipsilateral cancers in the same quadrant; of which two were local and two were local regional occurring 135, 106, 89, and 60 months after the initial diagnosis. All four patients had < 2 mm margins after initial surgery (p < 0.05).</p><p><strong>Conclusions: </strong>There is both an immediate (24.4%) and delayed (8.8%) risk of breast cancer in patients diagnosed with PLCIS and FLCIS. Our data support excision to 2 mm margin and maintenance of long-term follow-up.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"225-235"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599373","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}
引用次数: 0
Integrating large-scale in vitro functional genomic screen and multi-omics data to identify novel breast cancer targets. 整合大规模体外功能基因组筛选和多组学数据,以确定新的乳腺癌靶点。
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-01 DOI: 10.1007/s10549-025-07817-0
Hao-Kuen Lin, Jiawei Dai, Lajos Pusztai
{"title":"Integrating large-scale in vitro functional genomic screen and multi-omics data to identify novel breast cancer targets.","authors":"Hao-Kuen Lin, Jiawei Dai, Lajos Pusztai","doi":"10.1007/s10549-025-07817-0","DOIUrl":"https://doi.org/10.1007/s10549-025-07817-0","url":null,"abstract":"<p><strong>Purpose: </strong>Our goal is to leverage publicly available whole transcriptome and genome-wide CRISPR-Cas9 screen data to identify and prioritize novel breast cancer therapeutic targets.</p><p><strong>Methods: </strong>We used DepMap dependency scores > 0.5 to identify genes that are potential therapeutic targets in 48 breast cancer cell lines. We removed genes that were pan-essential or were not expressed in TCGA breast cancer cohort. Genes were prioritized based on druggability using the Drug-Gene Interaction Database. Targets were defined separately for ER+, HER2+, and TNBC. A broader list of genes with dependency score > 0.25 were used to assess the associations between dependency scores and mutations and copy number variations (CNV) to identify potential synthetic lethal relationships and to map survival critical genes into biological pathways.</p><p><strong>Results: </strong>66, 53, and 29 genes were prioritized as targets in ER+, HER2+, and TNBC, respectively. These included known actionable targets and many novel targets. ER+ included FOXA1, GATA3, LDB1, TRPS1, NAMPT, WDR26, and ZNF217; HER2+ cancers included STX4, HECTD1, and TBL1XR1; and TNBC included GFPT1 and GPX4. Synthetic lethal associations revealed 5 and 19 significant associations between potential survival critical genes and mutations in HER2+ and TNBC, respectively. For example, PIK3CA mutation increased dependency on NDUFS3 in HER2+ cancers, and CNTRL mutation increased dependency on electron transport chain (ETC) genes in TNBC. 329, 747, and 622 CNVs showed synthetic lethal association in ER+, HER2+, and TNBC, respectively.</p><p><strong>Conclusion: </strong>We provide a genome-wide drug target prioritization list for breast cancer derived from integrated large-scale omics data.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942816","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}
引用次数: 0
Repeat lumpectomy and external beam radiation therapy for ipsilateral breast cancer recurrence: a systematic review. 重复乳房肿瘤切除术和外束放疗治疗同侧乳腺癌复发:系统回顾。
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-01 Epub Date: 2025-07-16 DOI: 10.1007/s10549-025-07779-3
Shirley S W Tse, Caroline Hircock, Irene Karam, Hany Soliman, Shing Fung Lee, J Isabelle Choi, Jeffrey Q Cao, Tarek Hijal, Mylin Torres, Gustavo Nader Marta, Adrian W Chan, Danielle Rodin, C Anne Koch, Alyssa Wang, Edward Chow, Henry C Y Wong
{"title":"Repeat lumpectomy and external beam radiation therapy for ipsilateral breast cancer recurrence: a systematic review.","authors":"Shirley S W Tse, Caroline Hircock, Irene Karam, Hany Soliman, Shing Fung Lee, J Isabelle Choi, Jeffrey Q Cao, Tarek Hijal, Mylin Torres, Gustavo Nader Marta, Adrian W Chan, Danielle Rodin, C Anne Koch, Alyssa Wang, Edward Chow, Henry C Y Wong","doi":"10.1007/s10549-025-07779-3","DOIUrl":"10.1007/s10549-025-07779-3","url":null,"abstract":"<p><strong>Introduction: </strong>Salvage mastectomy is the standard of care for breast cancer patients with ipsilateral breast recurrence (IBR). This systematic review aims to evaluate effectiveness and safety of external beam RT (EBRT) as an accessible modality for repeat BCT.</p><p><strong>Methods: </strong>A systematic literature search was conducted on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from database inception until September 22, 2024. Clinical studies that investigated the use of second BCT (repeat BCS + post-operative RT) using EBRT were included.</p><p><strong>Results: </strong>Nine articles representing 8 studies and 569 patients were included. Most studies involved patients with T1 disease (6/8 studies, 75%), and node-negative recurrence (5/8 studies, 63%) partial breast re-irradiation was employed in a majority of studies (7/8 studies, 86%). The most common dose-fractionation schedule was 45 Gy in 30 twice-daily fractions (3/8 studies, 37%), followed by 50 Gy in 25 daily fractions (2/8 studies, 25%). The median follow-up ranged from 1.5 to 15 years. The average local recurrence rate was 10%. On average, grade 3 or worse acute and late skin and soft tissue toxicities were 1% and 3%, respectively. Only one study documented the incidence of long-term cardiac mortality (4% of patients) and one reported incidence of second malignancy (3% of patients). None of the included studies assessed patient-reported outcomes using validated quality of life questionnaires.</p><p><strong>Conclusion: </strong>Repeat BCT using EBRT is an emerging alternative to salvage mastectomy, offering favourable local control and acceptable rates of treatment-related toxicities.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"205-217"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648548","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}
引用次数: 0
Quantitative assessment of HER2 expression in invasive ductal carcinoma and co-existing DCIS. 浸润性导管癌及合并DCIS中HER2表达的定量分析。
IF 3 3区 医学
Breast Cancer Research and Treatment Pub Date : 2025-09-01 Epub Date: 2025-07-18 DOI: 10.1007/s10549-025-07781-9
Haiying Zhan, Nay Nwe Nyein Chan, Revekka Khaimova, Thazin N Aung, Patricia Gaule, Charles J Robbins, David L Rimm
{"title":"Quantitative assessment of HER2 expression in invasive ductal carcinoma and co-existing DCIS.","authors":"Haiying Zhan, Nay Nwe Nyein Chan, Revekka Khaimova, Thazin N Aung, Patricia Gaule, Charles J Robbins, David L Rimm","doi":"10.1007/s10549-025-07781-9","DOIUrl":"10.1007/s10549-025-07781-9","url":null,"abstract":"<p><strong>Purpose: </strong>Previous studies have demonstrated that ductal carcinoma in situ (DCIS) component often exhibits higher HER2 expression than the invasive component when assessed by immunohistochemistry, while some other studies showed concordant HER2 expression between these two components. In this study, we used our high-sensitivity HER2 (HS-HER2) quantitative immunofluorescence assay to compare HER2 expression in IDC and co-existing DCIS and correlate with clinicopathologic characteristics.</p><p><strong>Methods: </strong>We included 36 IDC + DCIS cases from the Yale Pathology department. DCIS was classified according to the three-tier nuclear grading system: low (grade 1), intermediate (grade 2), and high (grade 3) nuclear grade. Invasive carcinoma was graded according to the modified Bloom-Richardson histologic grading system. Cases were divided into two groups: low to intermediate-grade DCIS (G1-2) with co-existing invasive carcinoma (n = 26) and high-grade DCIS (G3) with co-existing invasive carcinoma (n = 10). Separate regions of interest for IDC and DCIS were annotated by two board-certified pathologists. Serial sections of FFPE tumor specimens were used to accurately measure the HER2 protein expression by the HS-HER2 assay in attomole/mm<sup>2</sup> unit and the acquisition by QuPath v.04 with the Qymia extension.</p><p><strong>Results: </strong>Low to intermediate-grade DCIS expressed higher HER2 levels (4295 ± 449 amol/mm<sup>2</sup>) than co-existing invasive carcinoma (2880 ± 413 amol/mm<sup>2</sup>). Similarly, high-grade DCIS expressed higher HER2 levels (4953 ± 700 amol/mm<sup>2</sup>) than co-existing invasive carcinoma (3560 ± 688 amol/mm<sup>2</sup>). Neither of these trends toward lower expression levels in the IDC were statistically significant. Additionally, no significant statistic difference was noted between low to intermediate-grade DCIS versus high-grade DCIS or between their corresponding co-existing invasive carcinomas in this cohort.</p><p><strong>Conclusion: </strong>Using the HS-HER2 assay, our results demonstrated comparable HER2 expression levels in DCIS and paired invasive carcinoma regardless of histopathological grade or HER2 immunohistochemical score. These findings contributed to a more nuanced understanding of HER2 biology in early breast carcinogenesis and may inform future biomarker-driven therapeutic strategies.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"273-279"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658394","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}
引用次数: 0
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