Breast Cancer Therapy–Related Cardiac Dysfunction in Adult Women Treated in Routine Clinical Practice: A Population-Based Cohort Study

Abstract

Purpose Most women diagnosed with breast cancer are younger than 65 years of age. Population-based studies on cancer therapy–related cardiotoxicity have focused on older women. We sought to determine the risk of cardiotoxicity with breast cancer therapy in women with an age distribution representative of routine clinical practice. Methods This was a population-based retrospective cohort study including 14 regional cancer centers in Ontario, Canada. Adult women receiving chemotherapy for stage I to III breast cancer between 2007 and 2012 were included. Cancer treatment was categorized as follows: anthracycline-based chemotherapy without trastuzumab, trastuzumab with nonanthracycline chemotherapy, anthracyclines followed by trastuzumab (sequential therapy), and chemotherapy without anthracycline/trastuzumab (other chemotherapy). The primary outcome was a composite of hospitalization or emergency room visit for congestive heart failure (CHF), outpatient diagnosis of CHF, or cardiovascular death. A sensitivity analysis limited the outcomes to hospital-based CHF events. Cause-specific hazard models were used accounting for the competing risk of noncardiovascular death. Results Of 18,540 women included (median age, 54 years; interquartile range, 47 to 63 years), 79% were younger than age 65 years. The cumulative incidence of the primary outcome was 3.08% (95% CI, 2.81% to 3.36%) by 3 years of follow-up, whereas in an age-matched sample of Ontario women (n = 92,700) without breast cancer, it was 0.96% (95% CI, 0.89% to 1.04%). Compared with those receiving other chemotherapy, patients receiving trastuzumab with nonanthracycline chemotherapy and sequential therapy were at a higher risk of cardiotoxicity (hazard ratio, 1.76 [95% CI, 1.19 to 2.60] and 3.96 [95% CI, 3.01 to 5.22], respectively). Hospital-based CHF events were only increased with sequential therapy (hazard ratio, 1.86; 95% CI, 1.07 to 3.22). Conclusion In women with breast cancer and an age distribution representative of routine clinical practice, trastuzumab-based regimens, including those without anthracyclines, were associated with an increased risk of cardiotoxicity. Sequential therapy increased the risk of hospital-based CHF events.