Breast cancer (Tokyo, Japan)最新文献

{"title":"Annual report of national clinical database-breast cancer registry in 2023: systemic therapy for small breast cancer.","authors":"Shinsuke Sasada, Hiraku Kumamaru, Naoko Kinukawa, Takayuki Iwamoto, Masahiro Kawashima, Takaaki Konishi, Shigehira Saji, Naoko Sanuki, Kenta Tanakura, Masayuki Nagahashi, Minoru Miyashita, Masayuki Yoshida, Takayuki Kinoshita, Yasuaki Sagara, Naoki Niikura, Takanori Ishida, Naruto Taira","doi":"10.1007/s12282-026-01881-0","DOIUrl":"10.1007/s12282-026-01881-0","url":null,"abstract":"<p><p>This annual report of the National Clinical Database-Breast Cancer Registry (NCD-BCR) by the Japanese Breast Cancer Society presents nationwide breast cancer statistics for patients registered in Japan in 2023. Among 107,372 patients with breast cancer at 1317 institutions, 99.3% were females with a median age of 62 years. The distribution of the clinical stages was as follows: stage 0 (15.5%); stage I (42.1%); stage II (31.1%); stage III (7.0%); and stage IV (2.1%). Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity was observed in 78.9%, 70.0%, and 13.3% of patients, respectively. Among 102,717 patients without distant metastases, 41.2% underwent breast-conserving surgery, 76.5% underwent sentinel lymph node biopsy, and 6.0% underwent breast reconstruction. The distribution of radiotherapy was as follows: 75.2% received whole-breast irradiation, 15.7% chest-wall irradiation, and 20.7% regional irradiation. Among the 13,061 patients with pT1abN0M0 breast cancer, comprising 10,819 hormone receptor [HR]-positive/HER2-negative, 1479 HER2-positive and 763 HR-negative/HER2-negative individuals, 92.4% of HR-positive/HER2-negative patients received endocrine therapy, 46.9% of HER2-positive patients received chemotherapy and/or anti-HER2 therapy, and 31.2% of HR-negative/HER2-negative patients received chemotherapy. This annual report provides a nationwide overview of contemporary systemic therapy patterns in small breast cancer and highlights size‑dependent and subtype‑specific use of systemic therapy in Japan, reflecting a risk‑adapted treatment strategy.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"947-953"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality-of-life assessment in the randomized JBCRG-M06/EMERALD study of eribulin plus dual HER2 blockade in HER2-positive locally advanced or metastatic breast cancer.","authors":"Tsuguo Iwatani, Norikazu Masuda, Shigehira Saji, Takuhiro Yamaguchi, Yasuyuki Kojima, Masahiro Kitada, Hiroshi Tada, Tsutomu Iwasa, Kei Koizumi, Hideo Shigematsu, Yasuaki Sagara, Toshitaka Okuno, Yoshie Hasegawa, Eriko Tokunaga, Tadahiko Shien, Uhi Toh, Hiroki Hasegawa, Shun Osaka, Satoshi Morita, Toshinari Yamashita","doi":"10.1007/s12282-026-01876-x","DOIUrl":"10.1007/s12282-026-01876-x","url":null,"abstract":"<p><strong>Background: </strong>Although taxanes are a mainstay treatment for locally advanced or metastatic breast cancer (LABC/MBC), they often impair quality of life (QoL). Treatments that avoid taxane-related QoL deteriorations would be valuable.</p><p><strong>Methods: </strong>The JBCRG-M06/EMERALD trial (NCT03264547, UMIN000027938) compared eribulin with a taxane, each combined with trastuzumab and pertuzumab, in patients with human epidermal growth factor receptor type 2 (HER2)-positive LABC/MBC. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module C30 (EORTC QLQ-C30) version 3.0. QoL deterioration was defined as a decrease in the Global Health Status (GHS) score by ≥ 10 points (minimum clinically important difference), disease progression, or death.</p><p><strong>Results: </strong>QoL data were available for 210 (of 224 randomized) and 205 (of 222 randomized) patients in the eribulin and taxane groups, respectively. The median (95% confidence interval) time to QoL deterioration was 7.16 (6.28-8.34) months in the eribulin group versus 4.57 (4.17-6.14) months in the taxane group, with a hazard ratio of 0.80 (95% confidence interval 0.65-0.98; log-rank P = 0.08). QoL was maintained at 6 and 12 months in greater proportions of the eribulin group (62.7% and 30.5%) compared with the taxane group (43.5% and 25.5%). GHS scores remained stable over time in the eribulin group. GHS deteriorated between weeks 9 and 27 in the taxane group (i.e. during treatment) with subsequent recovery toward baseline.</p><p><strong>Conclusions: </strong>Eribulin could help avoid the early deteriorations in QoL that occur during taxane therapy and maintain QoL for longer in patents with HER2-positive LABC/MBC receiving trastuzumab and pertuzumab.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1036-1046"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in CD8-positive lymphocytes following chemotherapy with concomitant bevacizumab in HER2-negative breast cancer.","authors":"Eriko Narusawa, Ayaka Katayama, Yukio Koibuchi, Daisuke Takata, Chikako Kanno Honda, Sayaka Obayashi, Sasagu Kurozumi, Daisuke Takahari, Ken Shirabe","doi":"10.1007/s12282-026-01869-w","DOIUrl":"10.1007/s12282-026-01869-w","url":null,"abstract":"<p><strong>Background: </strong>Bevacizumab is an anti-angiogenic agent that inhibits tumor vascularization and thereby suppresses tumor growth. Tumor-infiltrating lymphocytes (TILs), particularly CD8-positive TILs, play a critical role in the antitumor immune response. However, little is known about the effect of bevacizumab-containing chemotherapy on CD8-positive TIL dynamics. This study aimed to evaluate changes in CD8-positive TILs before and after treatment in patients with advanced breast cancer receiving bevacizumab in combination with chemotherapy.</p><p><strong>Methods: </strong>Thirty patients with initially inoperable advanced breast cancer who responded to first-line bevacizumab-containing chemotherapy and subsequently became eligible for surgery were included. CD8-positive TILs were assessed by immunohistochemistry in biopsy samples obtained before treatment and in surgical specimens collected after treatment. Stromal CD8-positive TILs were classified as low, intermediate, or high, based on their proportion among total stromal TILs.</p><p><strong>Results: </strong>Of the 30 patients, 20 had luminal-like breast cancer and 10 had triple-negative breast cancer. Before treatment, CD8-positive TIL expression was low in 16 patients (64.0%), intermediate in 6 (24.0%), and high in 3 (12.0%). After treatment, 10 patients (33.3%) showed low expression, 11 (36.7%) had intermediate expression, and 9 (30.0%) had high expression, indicating an increase in CD8-positive TIL levels. The high pathological response (a pathological response grade of 2 or higher) rate was 36.7%, and patients with increased CD8-positive TILs tended to show higher pathological response and better overall survival, although these differences did not reach statistical significance. In contrast, the ypT stage was significantly lower in cases with high post-treatment CD8-positive TIL expression, suggesting that immune activation after bevacizumab may contribute to local tumor regression.</p><p><strong>Conclusions: </strong>Bevacizumab-containing chemotherapy appears to enhance CD8-positive TIL infiltration in primary breast tumors, which may contribute to improved local tumor regression and better therapeutic outcomes.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1014-1020"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of BRCA2 variants of uncertain significance identified in Korean breast cancer patients.","authors":"Ah Reum Lim, Seung Pil Jung, Kyoungmi Kim, Hye Jin Choi, Kyong Hwa Park, Soohyeon Lee","doi":"10.1007/s12282-026-01886-9","DOIUrl":"10.1007/s12282-026-01886-9","url":null,"abstract":"<p><strong>Background: </strong>Variants of uncertain significance (VUS) in BRCA2 remain a major challenge in the clinical management of breast cancer, particularly in Asian populations where population-specific reference data are limited. Functional assays may provide complementary biological evidence to support interpretation of these variants.</p><p><strong>Patients and methods: </strong>Three BRCA2 missense VUS-c.5969 A > C (p.Asp1990Ala), c.3671G > A (p.Gly1224Asp), and c.5459G > A (p.Cys1820Tyr)-were selected based on their frequency in Korean cohorts and/or strong family history of breast cancer. Full-length BRCA2 constructs harboring each variant were introduced into BRCA2-knockout DLD-1 cells. Functional consequences were evaluated using cellular sensitivity assays following cisplatin treatment and ionizing radiation, response to the PARP inhibitor olaparib, and homologous recombination (HR) efficiency assessed by a GFP-based reporter system.</p><p><strong>Results: </strong>Cells expressing BRCA2 p.Asp1990Ala consistently demonstrated increased sensitivity to cisplatin, ionizing radiation, and olaparib, comparable to pathogenic controls. In addition, GFP-based HR assays revealed a marked reduction in HR repair efficiency in p.Asp1990Ala-expressing cells. In contrast, cells expressing BRCA2 p.Gly1224Asp or p.Cys1820Tyr exhibited DNA damage responses, drug sensitivity profiles, and HR activity similar to wild-type BRCA2 across all assays.</p><p><strong>Conclusions: </strong>Among the three BRCA2 VUS analyzed, p.Asp1990Ala exhibited a pathogenic-like functional phenotype characterized by impaired homologous recombination repair, whereas p.Gly1224Asp and p.Cys1820Tyr appeared functionally neutral. These findings highlight the functional heterogeneity of BRCA2 VUS and support the role of functional assays as complementary tools for variant interpretation in breast cancer.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1118-1128"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis of ER-positive, HER2-negative postmenopausal early breast cancer patients based on response to neoadjuvant endocrine therapy and multigene assay results: findings from the NEOS trial.","authors":"Hiroji Iwata, Norikazu Masuda, Yutaka Yamamoto, Tomomi Fujisawa, Tatsuya Toyama, Masahiro Kashiwaba, Shoichiro Ohtani, Naruto Taira, Takehiko Sakai, Yoshie Hasegawa, Rikiya Nakamura, Takuhiro Yamaguchi, Kentaro Sakamaki, Christy A Russell, Naoko Sugiyama","doi":"10.1007/s12282-026-01862-3","DOIUrl":"10.1007/s12282-026-01862-3","url":null,"abstract":"<p><strong>Background: </strong>We previously reported the 21-gene Oncotype DX® assay results from TransNEOS in patients enrolled in the phase 3 NEOS trial. However, the association between assay results and long-term prognosis has remained unclear.</p><p><strong>Methods: </strong>Of the 296 patients registered in TransNEOS, 226 patients were enrolled in this study. Multigene assay results were categorized into three groups based on Recurrence Score® (RS): RS low < 11, RS intermediate 11-25, RS high > 25. Kaplan-Meier methods evaluated the association between RS results and DDFS and OS across treatments and clinical response to neoadjuvant endocrine treatment (NET).</p><p><strong>Results: </strong>The clinical efficacy of NET was judged as CR, PR, and SD in 4 (1.8%), 113 (50%), and 109 (48.2%) patients, respectively. In the RS low and intermediate groups, no statistically significant difference in DDFS or OS was observed between the endocrine therapy (ET) alone group and the chemoendocrine therapy (CT + ET) group. In the RS high group, OS was significantly lower in the ET group compared to the CT + ET group (p = 0.037). Among patients in the RS high group who achieved CR + PR response to NET, there was no significant difference in OS between the CT + ET group and the ET alone group (p = 0.25). However, the number of events was limited, and the study may have been underpowered to detect a meaningful difference.</p><p><strong>Conclusions: </strong>The need for chemotherapy in postmenopausal HR + , HER2- breast cancer patients might be further informed by integrating the results of the Oncotype DX test with the response to NET.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1004-1013"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying breast cancer subtypes and exploring spatial expression patterns of the key subtype-specific gene based on pathological images, single-cell sequencing, and spatial transcriptomic data.","authors":"Ling-Gen Xiong, Xing-Feng Tu, Xiu-Ping Zheng, Rong-Nian Guo, Xin-Jing Li, Ming-Zhu Qiu, Rong-Kun Liang, Xiao-Hua Zhuo","doi":"10.1007/s12282-026-01883-y","DOIUrl":"10.1007/s12282-026-01883-y","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) is a heterogeneous disease. Accurate prognosis and molecular subtypes are critical for personalized treatment in BRCA. This study aimed to identify prognostic subtypes of BRCA based on features derived from pathological images and to explore their potential molecular and cellular mechanisms using spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq).</p><p><strong>Methods: </strong>Hematoxylin and eosin (H&E)-stained images were obtained from the TCGA-BRCA dataset using the OTSU algorithm. Pathological features were extracted using PyRadiomics. Feature selection was performed via Cox regression and machine learning. Subtypes were defined through consensus clustering, followed by differential gene expression. Key genes were identified using WGCNA and Lasso regression analysis. The spatial distribution and cellular interactions of key genes were analyzed by integrating ST and scRNA-seq datasets.</p><p><strong>Results: </strong>Among 1,406 extracted pathological features, 25 core features were identified, based on which two BRCA subtypes were defined. The C1 subtype was associated with advanced disease and poor prognosis. ESRP1 was identified as a key gene upregulated in the C1 subtype. ST analysis revealed that ESRP1 was highly expressed in tumor lesion areas and co-localized with epithelial and fibroblast cells. Cell-cell communication analysis revealed that fibroblasts served as central hubs in the TGF-β signaling network, particularly in regions enriched with ESRP1.</p><p><strong>Conclusions: </strong>This study identified pathology-derived prognostic BRCA subtypes that complement existing molecular classifications. The core gene, ESRP1, exhibited distinct spatial expression patterns in BRCA tissues, primarily localized to tumor core regions enriched with fibroblast cells. These findings provide exploratory insights into BRCA heterogeneity and potential therapeutic targets.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1102-1117"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interobserver reproducibility of macroscopic classification of breast cancer from representative cut surface of resected specimens and hematoxylin-eosin-stained slides.","authors":"Akiyoshi Hoshino, Yasuyo Ohi, Rin Yamaguchi, Hitoshi Tsuda, Ichiro Maeda","doi":"10.1007/s12282-026-01888-7","DOIUrl":"10.1007/s12282-026-01888-7","url":null,"abstract":"<p><strong>Background: </strong>Characteristics in shape and margins detected with diagnostic imaging are key features of breast cancers, but consensus on the criteria for macroscopic classification of breast cancer has yet to be established. The General Rules for Clinical and Pathological Recording of Breast Cancer, 19th edition, of Japan has adopted a macroscopic classification of breast cancer.</p><p><strong>Methods: </strong>Four breast pathologists evaluated the interobserver agreement level of the macroscopic classification for breast cancer cases using macroscopic photographs of cut surfaces of resected specimens and their overview images of hematoxylin-eosin-stained slides, which were provided from the pathology database of three facilities. From macroscopic shape and margins, these cases were classified into four types: non-mass, expansive, infiltrative, and mixed. Criteria for each type were established for the training set (n = 60), and then four pathologists independently classified 105 cases as the validation set. Interobserver agreement levels were calculated with kappa statistics.</p><p><strong>Results: </strong>In the validation set, consensus types were non-mass, expansive, infiltrative, and mixed in 18, 22, 25, and 35 cases, respectively. The four observers gave unanimous types for 47 cases (45%), and three or more observers gave concordant types for 78 cases (74%). An agreement level among the four observers was moderate (kappa = 0.561) in total, but the agreement levels between consensus types and observer-assigned types were always substantial (kappa = 0.690-0.799).</p><p><strong>Conclusion: </strong>Although the interobserver agreement level of the classification was still moderate in total, setting more specific and quantitative criteria and further studies may enhance the reproducibility of the macroscopic classification.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1129-1137"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indocyanine green fluorescence angiography algorithm for determining additional anastomosis in deep inferior epigastric perforator flap for breast reconstruction.","authors":"Rie Hayasaka, Kenta Tanakura, Yukiko Kuramoto, Tomohiro Imai","doi":"10.1007/s12282-026-01901-z","DOIUrl":"10.1007/s12282-026-01901-z","url":null,"abstract":"<p><strong>Background: </strong>Intraoperative indocyanine green (ICG) fluorescence angiography (ICG-FA) is commonly used to detect areas with poor perfusion. Fat necrosis caused by poor perfusion is often associated with the use of deep inferior epigastric perforator (DIEP) flaps. We report the development of an effective ICG-FA algorithm to prevent the occurrence of fat necrosis in the use of DIEP flaps.</p><p><strong>Methods: </strong>Fifty patients who underwent unilateral breast reconstruction using a DIEP flap and intraoperative ICG-FA were included. ICG-FA was performed after free-flap elevation to determine the extent of blood flow in the main perforating branch and the need for additional anastomosis (AA). Data on the presence of AA, vessels used, flap utilization rate, and postoperative course were collected and investigated.</p><p><strong>Results: </strong>AA was performed in 24 of the 50 patients (48%). The average flap utilization rates were 78.4% and 53.5% (p < 0.001) in the AA and non-AA groups, respectively. The probability of AA increased significantly when the flap utilization rate was > 70%. Seven types of AA were identified. The most common vessels used for AA were the contralateral deep inferior epigastric artery and vein. Postoperatively, localized fat necrosis was observed in only one case (2%) in the AA group.</p><p><strong>Conclusion: </strong>Our ICG-FA algorithm was useful for minimizing the occurrence of fat necrosis and aiding the use of extensive DIEP flaps without complications, leading to better functional results for patients.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1206-1213"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generalizability and reproducibility challenges in morphometric assessment of nuclear atypia in breast cancer.","authors":"Kadri Altundag","doi":"10.1007/s12282-026-01894-9","DOIUrl":"10.1007/s12282-026-01894-9","url":null,"abstract":"","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1239"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148538005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BARD1 and breast cancer genetic predisposition: case-control study and HRD signature analysis.","authors":"Marie-Florence Reveneau, Antoine De Pauw, Julien Masliah-Planchon, Antoine Decees, Salma Lakhlifi, Justine Pasanisi, Jessica Le Gall, Mathias Schwartz, Mélanie Pagès, Elise Pierre-Noël, Molka Sebai, Sandrine M Caputo, Virginie Moncoutier, Henrique Tenreiro, Christelle Berthemin, Jennifer Carrière, Catherine Dubois d'Enghien, Khadija Abidallah, Christophe Guy, Nicolas Fort, Narjes Zaguia, Anaïs Curto Taribo, Olfa Trabelsi Grati, Leslie Lori, Arnaud Maillard, Camille Benoist, Eleonore Frouin, Kévin Merchadou, Fabien Quinquis, Mathilde Filser, Hélène Delhomelle, Marine Le Mentec, Mathilde Warcoin, Ophélie Bertrand, Marie-Charlotte Villy, Claire Saule, Emmanuelle Mouret-Fourme, Marion Gauthier-Villars, Bruno Buecher, Tatiana Popova, Marc-Henri Stern, Victor Renault, Eric Pasmant, Dominique Stoppa-Lyonnet, Chrystelle Colas, Lisa Golmard","doi":"10.1007/s12282-026-01898-5","DOIUrl":"10.1007/s12282-026-01898-5","url":null,"abstract":"<p><strong>Introduction: </strong>BARD1 germline pathogenic variants (gPV) have been primarily associated with moderate breast cancer risk but their rarity limits accurate risk assessment and tailored follow-up guidelines. Our study evaluates the association between BARD1 gPV and breast cancer while exploring the role of BARD1 in mammary oncogenesis.</p><p><strong>Materials and methods: </strong>In this case-control study, 7,309 women with breast cancer and no gPV identified in the French hereditary breast and ovarian cancer (HBOC) gene panel at the Institut Curie were compared to 57,681 female controls from the gnomAD European non-cancer database. Tumors were analyzed for biallelic BARD1 inactivation and homologous recombination deficiency (HRD).</p><p><strong>Results: </strong>A significant association was observed between BARD1 gPV and breast cancer (OR = 5.2, 95% CI [3-8.9], p = 5.9 × 10^- 9). Molecular data were obtained and interpretable for seven tumors. Among these, two triple-negative (TN) primary tumors exhibited both biallelic BARD1 inactivation via loss of heterozygosity (LOH) and an HRD phenotype; one metastasis displayed LOH without HRD. All non-TN primary tumors lacked both biallelic inactivation and HRD.</p><p><strong>Conclusion: </strong>We found a strong enrichment of BARD1 gPV among women selected for personal and family history of breast cancer, reinforcing their relevance for genetic testing for suspected hereditary predisposition. Tumor analysis suggests a potential association between biallelic inactivation of BARD1 and the HRD phenotype in TN primary breast tumors, providing new treatment perspectives.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"1183-1193"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148582019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}