An Exploratory Study to Determine Whether BRCA1 and BRCA2 Mutation Carriers Have Higher Risk of Cardiac Toxicity

Genes

Michael Fradley¹  Xiuhua Zhao²  Roohi Ismail-Khan²  Jongphil Kim²  Weihong Sun²  Monique Sajjad²  Tuya Pal² 

[1] Division of Cardiovascular Medicine, University of South Florida, Tampa, FL, 33620, USA;Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612 USA;

关键词: Anthracycline-related cardiac toxicity;    BRCA1 mutation;    BRCA2 mutation;    conduction abnormalities;    heart failure;   

DOI  :  10.3390/genes8020059

来源: DOAJ

【 摘 要 】

Anthracycline-based cardiotoxicity is concerning for women with breast cancer and portends a dose-dependent risk of developing left ventricular dysfunction. Overall, the prevalence of heart failure (HF) is ≈2% of the total US population; however, BRCA-deficient mice have shown increased HF. We evaluated for the inherent risk of HF in women with BRCA mutations to determine whether treatment with anthracycline-based therapy increased this risk. We obtained results on BRCA mutation carriers regarding cancer treatment and HF, identified through the BRCA patient advocacy organization Facing Our Risk for Cancer Empowered (FORCE) and the Moffittbased Inherited Cancer Registry. In our patient group (232 BRCA1 and 159 BRCA2 patients; 10 with both mutations), 7.7% reported HF, with similar proportions in BRCA1 versus BRCA2 carriers (7.4% and 8.2%, respectively). These proportions are significantly higher than published rates (p < 0.001). There was no statistically significant difference in HF rates comparing anthracycline-treated versus anthracycline-naïve patients however (7.1% vs. 8.3%; p = 0.67). In addition, 9.1% of BRCA1 carriers and 8.2% of BRCA2 carriers reported arrhythmias. BRCA mutation carriers showed increased risk of cardiotoxicity versus the general population and an overall increased risk of cardiotoxicity from anthracycline-based therapy. Our study supports data that BRCA carriers have increased noncancer mortality from cardiotoxicity. A prospective trial to determine HF and conduction abnormalities in this population is warranted.

【 授权许可】

Unknown