reports

Long-term risk of heart failure associated with adjuvant trastuzumab in breast cancer patients

2014 American Society of Clinical Oncology Annual Meeting. Abstract 9504. J Clin Oncol 32 (suppl; abstr 9504).

University of Toronto, Toronto, ON, Canada; St. Michael’s Hospital, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; Princess Margaret Cancer Centre, Toronto, ON, Canada; Kingston General Hospital, Kingston, ON, Canada; Cancer Care Ontario, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Background: The late cardiac effect of adjuvant trastuzumab (T) and its potential interaction with anthracycline in the general population have not been well studied. The purpose of this retrospective population-based cohort study was to determine the long-term risk of heart failure (HF) associated with adjuvant T and chemotherapy, compared to chemotherapy alone.

Methods: Female breast cancer patients in Ontario, diagnosed between 2003 and 2009 were identified by the Ontario Cancer Registry and linked to administrative databases to ascertain demographics, cardiac risk factors, comorbidities, and use of adjuvant T and other chemotherapy. Patients with pre-existing HF were excluded. The main endpoint was new diagnosis of HF, obtained using an algorithm of admission and physician claims data. Group differences were assessed by the Kaplan-Meier (KM) method and multivariable piecewise Cox regression. Competing risk analysis using the Fine and Gray method and propensity score matching analysis were performed.

Results: 19,074 women with breast cancer treated with adjuvant chemotherapy were identified, of whom 3 371 (17.7%) also received adjuvant T. Anthracycline use was 84.9% overall. The groups did not differ significantly in demographics, comorbidities, or cardiac risk factors. After a median follow-up of 5.9 years, patients treated with T and chemotherapy were more likely to develop HF than patients on chemotherapy alone (5-year KM estimates of 5.3% vs. 2.6%; p<.0001 (log-rank)). After adjusting for confounders, adjuvant T remained independently associated with incident HF in the first 1.5 years (HR=5.77,95% CI 4.38-7.62,p=.0004),but not thereafter (HR=0.87,95% CI 0.57=1.33,p=0.53). Anthracycline did not increase the risk of HF with T synergistically (interaction p=0.23). Competing risk and propensity score analyses revealed similar results.

Conclusions: In this large population-based cohort study of breast cancer patients with long-term follow-up, adjuvant T was associated with increased risk of HF in breast cancer survivors, within the first 1.5 years of initiating treatment, but not thereafter. This provides reassurance about the long-term cardiac safety of adjuvant T in the general population.