Impact of stopping trastuzumab in early breast cancer: a population-based study in Ontario, Canada

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 — Retrospective population-based cohort study of early BC patients treated with adjuvant trastuzumab in Ontario, Canada, 2007-2016. Four groups were analyzed: A-full treatment, 17-18 cycles trastuzumab; B-Cardiac event within treatment period; C – ≤16 cycles, no cardiac events, stopped ≤30 days from last cardiac imaging (CI); D – ≤16 cycles, no cardiac events, stopped >30 days from CI. Primary outcome: disease-free survival; secondary outcomes: overall survival, cancer-specific, and cardiovascular mortality. Sensitivity analyses were performed 14 months after cycle 1 trastuzumab to control for early relapse.

Results — 5547 patients met inclusion criteria; A: 3921, B: 309, C: 362 and D: 955. 5-year DFS was 94.1% in group A, 80.1% group B, 81.4% group C and 82.4% group D. Using a Cox model, HR (95% CI) for 5-year DFS was 3.15 (2.13-4.65) for group B, 1.94 (1.30 – 2.89) group C and 1.92 (1.46-2.53) 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 one year of adjuvant trastuzumab in early stage BC.