title: The Temporal Risk of Heart Failure Associated With Adjuvant Trastuzumab in Breast Cancer Patients: A Population Study.
abstract: BACKGROUND
  The late cardiac effect of adjuvant trastuzumab and its potential interaction with anthracycline have not been well-studied on a population level.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Nineteen 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).
  
  
  CONCLUSIONS
  Adjuvant 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.
authors.affiliation: : 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).
authors.forename: Hart A
authors.initials: HA
authors.lastname: Goldhar
authors.affiliation: : 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).
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Yan
authors.affiliation: : 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).
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Ko
authors.affiliation: : 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).
authors.forename: Craig C
authors.initials: CC
authors.lastname: Earle
authors.affiliation: : 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).
authors.forename: George A
authors.initials: GA
authors.lastname: Tomlinson
authors.affiliation: : 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).
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Trudeau
authors.affiliation: : 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).
authors.forename: Murray D
authors.initials: MD
authors.lastname: Krahn
authors.affiliation: : 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).
authors.forename: Monika K
authors.initials: MK
authors.lastname: Krzyzanowska
authors.affiliation: : 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).
authors.forename: Raveen S
authors.initials: RS
authors.lastname: Pal
authors.affiliation: : 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).
authors.forename: Christine
authors.initials: C
authors.lastname: Brezden-Masley
authors.affiliation: : 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).
authors.forename: Scott
authors.initials: S
authors.lastname: Gavura
authors.affiliation: : 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).
authors.forename: Kelly
authors.initials: K
authors.lastname: Lien
authors.affiliation: : 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). kelvin.chan@sunnybrook.ca.
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: Chan
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009864:Ontario / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017741:Survivors / Q000706:statistics & numerical data; D013997:Time Factors; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D000068878:Trastuzumab