Management strategies and clinical outcomes in breast cancer patients who develop left ventricular dysfunction during trastuzumab therapy

Abstract

Background: Trastuzumab reduces risk of breast cancer recurrence but carries risk of cardiotoxicity that may be reversible upon treatment cessation and institution of left ventricular (LV) enhancement therapies (LVETx). We assessed management patterns of trastuzumab-induced cardiotoxicity (TIC) in a contemporary real-world setting. Methods: We reviewed charts of all breast cancer patients who received adjuvant trastuzumab in British Columbia between January 2010 and December 2013, spanning the opening of a cardio-oncology clinic. LV dysfunction (LVD) was classified as minimal (LVEF nadir 45–49%), mild (40–44%) or moderate-severe (< 40%). Charts were reviewed for baseline characteristics, management strategies, and outcomes. Multivariable analysis was performed to identify patient characteristics associated with trastuzumab completion and cardiology referral. Results: Of 967 patients receiving trastuzumab, 171 (17.7%) developed LVD, including 114 patients (11.8%) with LVEF declines of ≥10 to < 50%. Proportions of patients receiving cardiology referrals and LVETx increased and wait times to consultation decreased after a dedicated cardio-oncology clinic opened. LVETx was used more frequently in patients with moderate-severe LVD compared to minimal or mild LVD. Factors associated with completion of trastuzumab included mastectomy (OR 5.1, 95% CI 1.1–23.0) and proximity to quaternary care centre (OR 7.7, 95% CI 2.2–26.2). Moderate-severe LVD was associated with a lower probability of completing trastuzumab (OR 0.07 vs. minimal LVD, 95% CI 0.01–0.74). Factors associated with cardiology referral included heart failure symptoms (OR 8.0, 95% CI 1.5–42.9), proximity to quaternary care centre (OR 6.8, 95% CI 1.3–34.2), later year of cancer diagnosis (OR 2.4 per year, 95% CI 1.4–4.3), node-positive disease (OR 0.18, 95% CI 0.06–0.56), mastectomy (OR 0.05, 95% CI 0.01–0.52), and minimal LVD (OR 0.14, 95% CI 0.05–0.46). LVEF recovered to > 50% in 90.7% of patients. Conclusions: Management strategies in patients with TIC are associated with cancer characteristics and severity of cardiotoxicity. Access to dedicated cardio-oncology clinics may facilitate optimal care of this complex patient population.