{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:46:12Z","timestamp":1782708372275,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2017C03013"],"award-info":[{"award-number":["2017C03013"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFE0198800"],"award-info":[{"award-number":["2019YFE0198800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017538","name":"Zhejiang Provincial Ten Thousand Plan for Young Top Talents","doi-asserted-by":"publisher","award":["2021R52020"],"award-info":[{"award-number":["2021R52020"]}],"id":[{"id":"10.13039\/501100017538","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Global advances in genetic testing are reshaping breast cancer management. Although large unselected Chinese cohorts have been reported, the\n                      <jats:italic>BRCA1<\/jats:italic>\n                      and\n                      <jats:italic>BRCA2<\/jats:italic>\n                      (\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      ) variant landscape specifically in high-risk, clinically referred populations remains poorly characterized. We aimed to delineate the landscape of\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      variants in high-risk Chinese breast cancer patients, consistent with the clinical referral and testing pathway, and to provide evidence to inform risk-adapted clinical practice for high-risk patients with breast cancer in eastern China.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed 1,262 high-risk Chinese breast cancer patients using targeted next-generation sequencing to detect\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      germline variants. Variant clinical significance was interpreted primarily based on ClinVar annotations within the ACMG\u2013AMP 2015 framework, with population frequency and in silico prediction results used as supporting evidence. Statistical analyses were performed in R (version 4.5.0).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 124 cases were identified as carriers of 81\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      P\/LP (pathogenic or likely pathogenic) variants. P\/LP carriers were more frequent in patients aged \u226445 years in our cohort. A total of 9.8% of patients carried\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      P\/LP variants, with 5.5% and 4.3% carrying\n                      <jats:italic>BRCA1<\/jats:italic>\n                      and\n                      <jats:italic>BRCA2<\/jats:italic>\n                      variants (70 vs. 54 cases), respectively. Among the 336 patients with triple-negative breast cancer (TNBC), 60 cases carried\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      P\/LP variants (51\n                      <jats:italic>BRCA1<\/jats:italic>\n                      vs. 9\n                      <jats:italic>BRCA2<\/jats:italic>\n                      ). A total of 21 variants were observed in more than one participant, including\n                      <jats:italic>BRCA1<\/jats:italic>\n                      c.5470_5477del, a founder mutation in Chinese populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Taken together, this study provides the most comprehensive characterization to date of the\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      variant landscape in a high-risk Chinese breast cancer cohort from mainland China, offering population-specific reference data to refine genetic counseling, screening prioritization, and risk management, with potential implications for targeted prevention and intervention in Chinese patients seen in clinical practice.\n                    <\/jats:p>\n                  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