{"doi":"10.3389/fcvm.2022.833171","title":"BRCA1/2 Mutations and Cardiovascular Function in Breast Cancer Survivors","abstract":"Objective Animal models suggest that BRCA1/2 mutations increase doxorubicin-induced cardiotoxicity risk but data in humans are limited. We aimed to determine whether germline BRCA1/2 mutations are associated with cardiac dysfunction in breast cancer survivors. Methods In a single-center cross-sectional study, stage I-III breast cancer survivors were enrolled according to three groups: (1) BRCA1/2 mutation carriers treated with doxorubicin; (2) BRCA1/2 mutation non-carriers treated with doxorubicin; and (3) BRCA1/2 mutation carriers treated with non-doxorubicin cancer therapy. In age-adjusted analysis, core-lab quantitated measures of echocardiography-derived cardiac function and cardiopulmonary exercise testing (CPET) were compared across the groups. A complementary in vitro study was performed to assess the impact of BRCA1 loss of function on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) survival following doxorubicin exposure. Results Sixty-seven women with mean (standard deviation) age of 50 (11) years were included. Age-adjusted left ventricular ejection fraction (LVEF) was lower in participants receiving doxorubicin regardless of BRCA1/2 mutation status ( p = 0.03). In doxorubicin-treated BRCA1/2 mutation carriers and non-carriers, LVEF was lower by 5.4% (95% CI; −9.3, −1.5) and 4.8% (95% CI; −9.1, −0.5), respectively compared to carriers without doxorubicin exposure. No significant differences in VO 2max were observed across the three groups (p overall = 0.07). Doxorubicin caused a dose-dependent reduction in viability of iPSC-CMs in vitro without differences between BRCA1 mutant and wild type controls ( p > 0.05). Conclusions BRCA1/2 mutation status was not associated with differences in measures of cardiovascular function or fitness. Our findings do not support a role for increased cardiotoxicity risk with BRCA1/2 mutations in women with breast cancer.","journal":"Frontiers in Cardiovascular Medicine","year":2022,"id":282020,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":631154,"name":"Wenjian Lv","orcid":null,"position":1,"is_corresponding":false},{"id":797223,"name":"Nicholas S. Wilcox","orcid":"0000-0002-3693-7650","position":2,"is_corresponding":false},{"id":957658,"name":"Karyn Sheline","orcid":"0000-0002-7401-0952","position":3,"is_corresponding":false},{"id":255206,"name":"Amanda M. Smith","orcid":"0000-0002-9881-236X","position":4,"is_corresponding":false},{"id":519048,"name":"Kathleen M. Sturgeon","orcid":"0000-0001-9602-7897","position":5,"is_corresponding":false},{"id":958142,"name":"Chris McDermott‐Roe","orcid":null,"position":6,"is_corresponding":false},{"id":258825,"name":"Kiran Musunuru","orcid":"0000-0003-3298-0368","position":7,"is_corresponding":false},{"id":255204,"name":"Bénédicte Lefebvre","orcid":"0000-0002-8587-7279","position":8,"is_corresponding":false},{"id":78635,"name":"Susan M. Domchek","orcid":"0000-0002-5914-7272","position":9,"is_corresponding":false},{"id":299780,"name":"Payal D. Shah","orcid":"0000-0001-5874-3390","position":10,"is_corresponding":false},{"id":282965,"name":"Bonnie Ky","orcid":"0000-0002-6628-9981","position":11,"is_corresponding":false},{"id":282964,"name":"Biniyam G. Demissei","orcid":"0000-0003-0875-4985","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-19T00:29:15.734856Z","pmid":"35242827","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}