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However, the chronology of genetic events during breast tumor evolution in\n                    <jats:italic>BRCA1<\/jats:italic>\n                    carriers remains unclear. In this study, 57 primary breast tumors from 57\n                    <jats:italic>BRCA1<\/jats:italic>\n                    carriers were analyzed, including formalin\u2010fixed paraffin\u2010embedded specimens and fresh\u2010frozen specimens. Formalin\u2010fixed paraffin\u2010embedded tumors were microdissected into normal mammary tissue, carcinoma in\u00a0situ, and invasive carcinoma components for deep target\u2010region sequencing, whereas fresh\u2010frozen tumors underwent whole\u2010exome sequencing and bulk transcriptome sequencing. Compared with non\u2010carriers from The Cancer Genome Atlas, breast cancers from\n                    <jats:italic>BRCA1<\/jats:italic>\n                    carriers showed a distinct mutational landscape characterized by a high prevalence of\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations and a reduced frequency of\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    and\n                    <jats:italic>GATA3<\/jats:italic>\n                    alterations. Based on the initiating driver event,\n                    <jats:italic>BRCA1<\/jats:italic>\n                    \u2010associated tumors were classified into three subgroups:\n                    <jats:italic>TP53<\/jats:italic>\n                    , PI(3)K\u2010AKT pathway, and unclassified. The\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010driven subgroup was strongly associated with the triple\u2010negative phenotype, loss of heterozygosity at the\n                    <jats:italic>BRCA1<\/jats:italic>\n                    locus, and elevated genomic instability.\n                    <jats:italic>TP53<\/jats:italic>\n                    truncating mutations were enriched in\n                    <jats:italic>BRCA1<\/jats:italic>\n                    carriers compared with non\u2010carriers and showed a trend toward worse outcomes, potentially related to lower homologous recombination deficiency scores and activation of epithelial\u2010mesenchymal transition pathways. These findings highlight the distinct mutational architecture of breast cancers from\n                    <jats:italic>BRCA1<\/jats:italic>\n                    carriers and suggest that\n                    <jats:italic>TP53<\/jats:italic>\n                    truncating mutations may define a particularly aggressive subtype that warrants further investigation.\n                  <\/jats:p>","DOI":"10.1111\/cas.70460","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:51:02Z","timestamp":1783122662000},"page":"2863-2876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Evolution in\n                    <i>BRCA1<\/i>\n                    \u2010Associated Breast Cancer Reveals Early Driver Mutations Shaping Tumor Features and Prognosis"],"prefix":"10.1111","volume":"117","author":[{"given":"Li","family":"Hu","sequence":"first","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiting","family":"Wan","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Liao","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyun","family":"Ding","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Meng","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wu","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"Familial &amp; Hereditary Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Peking University Cancer Hospital &amp; Institute  Beijing P. R. 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