title: The incidence of cardiomyopathy in BRCA1 and BRCA2 mutation carriers after anthracycline-based adjuvant chemotherapy.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Texas Oncology, Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, 3410 Worth Street, Suite 400, Dallas, TX, 75246, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearson
authors.affiliation: Texas Oncology, Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, 3410 Worth Street, Suite 400, Dallas, TX, 75246, USA.
authors.forename: Anju
authors.initials: A
authors.lastname: Nair
authors.affiliation: Baylor Scott and White Health, 8080 North Central Expressway, Suite 900, Dallas, TX, 75206, USA.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Daoud
authors.affiliation: Texas Oncology, Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, 3410 Worth Street, Suite 400, Dallas, TX, 75246, USA. Joanne.Blum@USOncology.com.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D009202:Cardiomyopathies / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D066126:Cardiotoxicity; D015897:Comorbidity; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018943:Anthracyclines
keywords: Anthracycline; BRCA1; BRCA2; Cardiotoxicity