ABSTRACT
BACKGROUND: Adjuvant trastuzumab for early-stage (I-III) HER2-positive breast cancer (BC) has led to statistically significant improvement in cancer outcomes but carries a risk of cardiotoxicity. Trastuzumab is discontinued early in many patients for asymptomatic changes in left ventricular ejection fraction. We evaluated the impact of early discontinuation of trastuzumab on cancer outcomes. METHODS: We conducted a retrospective population-based cohort study of early BC patients treated with adjuvant trastuzumab in Ontario, Canada, 2007-2016. Four groups were analyzed: group A was full treatment, 17-18 cycles trastuzumab; group B was cardiac event (CE) within treatment period; group C was ≤16 cycles, no CEs, stopped within 30 days from last cardiac imaging; and group D was ≤16 cycles, no CEs, stopped more than 30 days from cardiac imaging. Primary outcome was disease-free survival (DFS); secondary outcomes were: overall survival, cancer-specific mortality, and cardiovascular mortality. Sensitivity analyses were performed 14 months after cycle 1 trastuzumab to control for early relapse. RESULTS: A total of 5547 patients met the inclusion criteria: group A = 3921, group B = 309, group C = 362, and group D = 955. The 5-year DFS was 94.1% in group A, 80.1% in group B, 81.4% in group C, and 82.4% in group D. Using a Cox model, the hazard ratio for 5-year DFS was 3.15 (95% confidence interval [CI] = 2.13 to 4.65) for group B, 1.94 (95% CI = 1.30 to 2.89) for group C, and 1.92 (95% CI = 1.46 to 2.53) for group D. Overall, 26 patients (0.5%) died of cardiac causes. CONCLUSIONS: BC patients in Ontario who did not complete adjuvant trastuzumab had a statistically significantly higher risk of BC relapse and death and low incidence of cardiac death. These findings support 1 year of adjuvant trastuzumab in early-stage BC.
Subject(s)
Breast Neoplasms/drug therapy , Trastuzumab/administration & dosage , Trastuzumab/adverse effects , Withholding Treatment , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Cause of Death , Cohort Studies , Disease-Free Survival , Female , Heart Diseases/chemically induced , Heart Diseases/epidemiology , Heart Diseases/mortality , Humans , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/etiology , Neoplasm Staging , Ontario/epidemiology , Retrospective Studies , Stroke Volume/drug effects , Survival Analysis , Treatment Outcome , Ventricular Function, Left/drug effects , Withholding Treatment/statistics & numerical data , Young AdultABSTRACT
PURPOSE OF REVIEW: This paper will focus on novel breast cancer therapies used in clinical practice today, as well as review our understanding of standard therapies and their potential impact on cardiovascular health. RECENT FINDINGS: Established and novel treatments such as anthracyclines, HER2-targeted agents, and immunotherapy have contributed to improvements in breast cancer outcomes; however, these treatments may be associated with an increased risk of cardiovascular injury. The number of available breast cancer treatments continues to expand, as does the need for health care providers to understand the potential impact of these treatments on cardiovascular health. Collaborative approaches in the development of risk stratification, prevention, and surveillance strategies for patients exposed to established and novel breast cancer treatments will facilitate improvements in patient outcomes without compromising their cardiovascular health.
