Risk of Congestive Heart Failure Increased With Trastuzumab Use in Older Breast Cancer Patients
Risk and risk factors for congestive heart failure in older breast cancer patients receiving trastuzumab have not been clearly defined. In a study reported in the Journal of Clinical Oncology, Mariana Chavez-MacGregor, MD, of The University of Texas MD Anderson Cancer Center, and colleagues analyzed risks of congestive heart failure in a population of Medicare-covered women with stage I to III breast cancer treated with chemotherapy. Trastuzumab (Herceptin) use was significantly associated with congestive heart failure risk, and risk among trastuzumab users was increased in patients aged > 80 years, those with coronary artery disease or hypertension, and those who received weekly trastuzumab.
Study Details
The study involved breast cancer patients aged ≥ 66 years with full Medicare coverage diagnosed with stage I to III breast cancer between 2005 and 2009 and treated with chemotherapy who were identified from Surveillance, Epidemiology, and End Results (SEER)–Medicare and Texas Cancer Registry–Medicare databases. Chemotherapy, trastuzumab use, comorbidities, and congestive heart failure were identified using International Classification of Diseases (version 9) and Healthcare Common Procedure Coding System codes.
In total, 9,535 patients were included, 2,203 (23.1%) of whom received trastuzumab. The median age of the entire cohort was 71 years. Trastuzumab users had later year of diagnosis, older age, were less likely to have regional vs localized disease, less likely to have received radiation therapy, less likely to have received anthracyclines, and more likely to have received taxanes.
Increased Risk
Rates of congestive heart failure were 29.4% in trastuzumab users vs 18.9% in nonusers (P < .001). On multivariate analysis including age, race/ethnicity, year of diagnosis, stage, Charlson comorbidity score, anthracycline use, taxane use, hypertension, sex, tumor grade, hormone receptor status, surgery, and radiation therapy, trastuzumab use was still associated with significantly increased risk of congestive heart failure (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.75–2.17). Other significant predictors were age ≥ 76 years, black race/ethnicity, later year of diagnosis, Charlson comorbidity score, anthracycline use, and hypertension.
Factors Associated With Increased Risk
Among trastuzumab users, older age (HR = 1.53, 95% CI = 1.16–2.10, for age > 80 vs 66-70 years), coronary artery disease (HR = 1.82, 95% CI = 1.34–2.48), hypertension (HR = 1.24, 95% CI = 1.02–1.50), and weekly vs every-3-week trastuzumab administration (HR = 1.33, 95% CI = 1.05–1.68) were associated with significantly increased risk of congestive heart failure on multivariate analysis. Among trastuzumab users who developed congestive heart failure, 68.8% of the congestive heart failure events occurred within the first 12 months after initiation of treatment.
The investigators concluded: “In this large cohort of older breast cancer patients, the rates of trastuzumab-related [congestive heart failure] are higher than those reported in clinical trials. Among patients treated with trastuzumab, those with cardiac comorbidities and older age may be at higher risk. Further studies need to confirm the role that the frequency of administration plays in the development of trastuzumab-related congestive heart failure.”
The study was supported by the Center for Comparative Effectiveness Research on Cancer in Texas, the Nellie B. Connally Breast Cancer Research fund, and a grant from the American Cancer Society.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
