Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines

• Published in: Breast cancer research and treatment 2016-01, Vol.155 (2), p.285-293
• Main Authors: Barac, Ana, Lynce, Filipa, Smith, Karen L., Mete, Mihriye, Shara, Nawar M., Asch, Federico M., Nardacci, Madeline P., Wray, Lynette, Herbolsheimer, Pia, Nunes, Raquel A., Swain, Sandra M., Warren, Robert, Peshkin, Beth N., Isaacs, Claudine
• Format: Article
• Language: English
• Subjects: Adjuvant chemotherapy; Adult; Anthracyclines; Anthracyclines - adverse effects; Anthracyclines - therapeutic use; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Cardiovascular disease; Chemotherapy; Clinical Trial; Comparative analysis; Development and progression; Doxorubicin - therapeutic use; Female; Health aspects; Heart; Heart failure; Humans; Medicine; Medicine & Public Health; Middle Aged; Mutation; Mutation - genetics; Oncology; Prospective Studies; Side effects; Stroke Volume - drug effects; Toxicity; Ventricular Function, Left - drug effects
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-016-3678-2

Animal data suggest that defects in BRCA1/2 genes significantly increase the risk of heart failure and mortality in mice exposed to doxorubicine. Women with BRCA1/2 mutations who develop breast cancer (BC) may receive anthracyclines but their risk of cardiac dysfunction has not been investigated. Our study tested the hypothesis that women with history of BRCA1/2 mutation-associated BC treated with anthracyclines have impaired parameters of cardiac function compared to similarly treated women with history of sporadic BC. Women with history of BC and anthracycline treatment underwent an echocardiographic exam for assessment of primary outcomes, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). The sample size of 81 provided 79 % power with two-sided two-sample t test and alpha of 0.05 to detect a clinically meaningful difference in cardiac function of absolute 5 % points difference for LVEF and 2 % points difference for GLS. Of 81 normotensive participants, 39 were BRCA1/2 mutation carriers and 42 in the sporadic group. Mean age was 50 ± 9 years in both groups ( P  = 0.99) but BRCA1/2 mutation carriers had longer anthracycline treatment-to-enrollment time (7.5 ± 5.3 vs. 4.2 ± 3.3 years, P  = 0.001). There were no significant differences in LVEF ( P  = 0.227) or GLS ( P  = 0.53) between the groups. LVEF was normal in 91 % of women and subclinical cardiac dysfunction defined as absolute GLS value