Edward J Pearson1, Anju Nair1, Yahya Daoud2, Joanne L Blum3. 1. Texas Oncology, Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, 3410 Worth Street, Suite 400, Dallas, TX, 75246, USA. 2. Baylor Scott and White Health, 8080 North Central Expressway, Suite 900, Dallas, TX, 75206, USA. 3. 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.
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.
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-deficientmice and increased rates of heart failure in homozygous BRCA1-deficientmice following ischemic insult. Therefore, we conducted a retrospective matched cohort study to determine the rates of anthracycline-induced cardiomyopathy in breast cancerpatients 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 cancerpatients 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 cancerpatients 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 cancerpatients with BRCA1 and/or BRCA2 gene mutations treated with standard doses of anthracycline compared to the general population.
Authors: Angela H E M Maas; Giuseppe Rosano; Renata Cifkova; Alaide Chieffo; Dorenda van Dijken; Haitham Hamoda; Vijay Kunadian; Ellen Laan; Irene Lambrinoudaki; Kate Maclaran; Nick Panay; John C Stevenson; Mick van Trotsenburg; Peter Collins Journal: Eur Heart J Date: 2021-03-07 Impact factor: 29.983
Authors: Kyuwan Lee; Irene Kang; Wendy J Mack; Joanne Mortimer; Fred Sattler; George Salem; Christina M Dieli-Conwright Journal: BMC Cancer Date: 2019-07-03 Impact factor: 4.430
Authors: Biniyam G Demissei; WenJian Lv; Nicholas S Wilcox; Karyn Sheline; Amanda M Smith; Kathleen M Sturgeon; Chris McDermott-Roe; Kiran Musunuru; Bénédicte Lefebvre; Susan M Domchek; Payal Shah; Bonnie Ky Journal: Front Cardiovasc Med Date: 2022-02-15