Abstract
Purpose
Breast cancer remains the fourth-leading cause of death in the United States. Nearly 10% of breast cancers are hereditary, with deleterious mutations in BRCA1 and BRCA2 genes being the leading cause. Anthracycline chemotherapy, used commonly for breast cancer, carries cardiotoxicity risk. Recent studies demonstrated anthracycline-induced cardiac failure in homozygous BRCA2-deficient mice and increased rates of heart failure in homozygous BRCA1-deficient mice following ischemic insult. Therefore, we conducted a retrospective matched cohort study to determine the rates of anthracycline-induced cardiomyopathy in breast cancer patients with germline mutation in BRCA1 or BRCA2 genes compared to age-matched patients without a BRCA1 or BRCA2 gene mutation.
Methods
The primary endpoint was to determine the rate of cardiomyopathy defined as either congestive heart failure or asymptomatic decline in ejection fraction to <50%. A total of 102 breast cancer patients who were BRCA gene mutation carriers (55 BRCA1, 45 BRCA2, and two with both), who received anthracycline-based chemotherapy were compared to a matched cohort of breast cancer patients with wild-type BRCA gene status.
Results
We found a 4.9% rate of cardiomyopathy in the BRCA mutation carriers and 5.2% in the matched controls (p = 0.99). Cox proportional hazards model showed that only trastuzumab and hypertension were significantly associated with the development of cardiomyopathy in both groups (p < 0.05).
Conclusions
Given the limitations of a retrospective study, we saw no increased risk of cardiotoxicity among breast cancer patients with BRCA1 and/or BRCA2 gene mutations treated with standard doses of anthracycline compared to the general population.
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Acknowledgements
This study was supported, in part, by the Baylor University Medical Center, Charles A. Sammons Cancer Center Trainee Cancer Research Award.
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The authors declare that they have no conflict of interest.
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This study was approved by the Baylor Scott & White Institutional Review Board.
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Pearson, E.J., Nair, A., Daoud, Y. et al. The incidence of cardiomyopathy in BRCA1 and BRCA2 mutation carriers after anthracycline-based adjuvant chemotherapy. Breast Cancer Res Treat 162, 59–67 (2017). https://doi.org/10.1007/s10549-016-4101-8
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DOI: https://doi.org/10.1007/s10549-016-4101-8