• Hart A Goldhar, Andrew T Yan, Dennis T Ko, Craig C Earle, George A Tomlinson, Maureen E Trudeau, Murray D Krahn, Monika K Krzyzanowska, Raveen S Pal, Christine Brezden-Masley, Scott Gavura, Kelly Lien, and Kelvin K W Chan.
• : Faculty of Medicine, University of Toronto, Toronto, ON (HAG, ATY, DTK, CCE, GAT, MET, MDK, MKK, CB, KKWC); Division of Cardiology, St. Michael's Hospital, Toronto, ON (ATY); Institute for Clinical Evaluative Sciences, Toronto, ON (DTK, CCE, MKK); Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, ON (DTK); Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, ON (CCE, MET, KL, KKWC); Ontario Institute for Cancer Research, Toronto, ON (CCE); University Health Network, Toronto, ON (GAT, MKK); Toronto Health Economics and Health Assessment, Toronto, ON (MDK); Division of Hematology/Oncology, St. Michael's Hospital, Toronto, ON (CB); Department of Medicine, Queens University, and Cardiac Program, Kingston General Hospital, Kingston, ON (RSP); Cancer Care Ontario, Toronto, ON (SG).
• J. Natl. Cancer Inst. 2016 Jan 1; 108 (1).

BackgroundThe late cardiac effect of adjuvant trastuzumab and its potential interaction with anthracycline have not been well-studied on a population level.MethodsIn this retrospective population-based cohort study, 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 trastuzumab and other chemotherapy. Patients with pre-existing heart failure (HF) were excluded. The main endpoint was new diagnosis of HF. Analyses included Kaplan-Meier (KM) survival analysis, multivariable piecewise Cox regression, and competing risk and propensity score analyses. All statistical tests were two-sided.ResultsNineteen thousand seventy-four women with breast cancer treated with adjuvant chemotherapy were identified, of whom 3371 (17.7%) also received adjuvant trastuzumab. Anthracycline use was 84.9% overall. After a median follow-up of 5.9 years, patients treated with trastuzumab and chemotherapy were more likely to develop HF than patients on chemotherapy alone (5-year cumulative incidences of 5.2% vs 2.5%; log-rank P < .001). After adjusting for confounders, adjuvant trastuzumab remained independently associated with incident HF in the first 1.5 years (HR = 5.77, 95% CI = 4.38 to 7.62, P < .001), but not thereafter (HR = 0.87, 95% CI = 0.57 to 1.33, P = .53). Anthracycline use did not increase the risk of HF with trastuzumab synergistically, neither within (P interaction = .92) nor beyond 1.5 years (P interaction = .23).ConclusionAdjuvant trastuzumab was associated with increased risk of new incidence of HF in breast cancer survivors during the period of adjuvant treatment but not thereafter. Routine intensive monitoring may not be necessary after completing adjuvant therapy.© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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