Trastuzumab-related cardiotoxicity among older breast cancer patients.

Abstract

600 Background: The use of trastuzumab in the adjuvant setting is associated with reduction in mortality and recurrence. Although trastuzumab is extremely well tolerated, its use is associated with congestive heart failure (CHF). The incidence of this complication in the general population remains largely unknown, especially in older patients. In this study we evaluated the rates and risk factors associated with trastuzumab-related CHF in a large cohort of older breast cancer patients. Methods: Breast cancer patients ≥ 66 years with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005-2007, and treated with chemotherapy were identified in the Surveillance, Epidemiology and End Results-Medicare (SEER-Medicare) database. Chemotherapy and trastuzumab use, comorbidities and CHF were identified using ICD-9 and HCPCS codes. Analyses included descriptive statistics, Cox proportional hazard model using trastuzumab as a time-dependent variable and logistic regression. Results: A total of 3,983 patients were included, 847 (21.7%) of them received trastuzumab, median age of the entire cohort was 71 years old. Among trastuzumab users the rate of CHF was 28.6% compared to 18.1% in non-trastuzumab users (p<.0001). After adjusting for demographic and clinical characteristics, comorbidities, and type of chemotherapy used, trastuzumab users were more likely to develop CHF than non-trastuzumab users (HR 1.74; 95% CI 1.47-2.06). Among trastuzumab users, older age did not further increase the risk, however history of coronary artery disease (OR 2.23; 95%CI 1.56-3.19), heart valve disease (OR 1.41; 95%CI 1.41-2.88) and emphysema -as a proxy for smoking- (OR 2.03; 95% CI 1.13-3.63) significantly increased the risk of CHF. There was a trend for increased risk of CHF associated with anthracycline use (OR 1.36; 95% CI 0.93-2.00). Conclusions: In this large cohort of older breast cancer patients, the risk of CHF among trastuzumab users was 1.74 times higher than non-trastuzumab users, which is higher than what has been reported in younger clinical trial participants. Among older breast cancer patients treated with trastuzumab, cardiac comorbidities and emphysema may identify high risk patients.