Trastuzumab-Related Cardiotoxicity and Cardiac Care in Patients With HER2 Positive Metastatic Breast Cancer

Abstract

Prolonged trastuzumab therapy is the standard of care for women with metastatic HER2 positive (HER2+) breast cancer. There are limited data on the incidence of cardiotoxicity, its treatment implication, and cardiac care in these patients. We retrospectively identified consecutive women who received >12 months of trastuzumab treatment at Princess Margaret Cancer Centre (Toronto, ON) from 2007 to 2012 for metastatic HER2 positive breast cancer and followed them until death or August 2018. Patients were included if a pretherapy multigated acquisition scan and ≥2 subsequent follow-up scans were available. The Cardiac Review and Evaluation Committee Criteria were used to identify cardiotoxicity. Baseline characteristics and outcomes (final left ventricular ejection fraction, change in LVEF, trastuzumab interruption) were compared in patients with and without cardiotoxicity. Cardiac care and treatment received were recorded. Sixty patients (mean age 52 ± 10.4 years) were included. The median trastuzumab exposure was 37 cycles (interquartile range 23 to 56) over 28 months (interquartile range 19 to 49) and 48% received previous anthracycline therapy. The cumulative incidence of cardiotoxicity was 35% (95% CI 23 to 48) at 3 years. Patients who developed cardiotoxicity were more likely to receive third-line cancer treatments and had lower final LVEF than patients without (54.9% ± 6.3% vs 64% ± 4.9%, p <0.001). Of the 23 patients with cardiotoxicity, 10 (43%) had trastuzumab interrupted for at least 1 cycle, only 7 (30%) patients were seen by a cardiologist and 4 (17%) received cardiac medications. In conclusion, patients with metastatic breast cancer receiving prolonged trastuzumab therapy appear to have high rates of cardiotoxicity. This was associated with high rates of trastuzumab interruption, but low rates of cardiology referral and cardiac treatment, reflecting a potential cardiac care gap.