Trastuzumab-Induced Cardiotoxicity: Testing a Clinical Risk Score in a Real-World Cardio-Oncology Population

Background: Trastuzumab has improved survival for women with HER2-positive breast cancer, but its use is associated with an increased risk of cardiotoxicity. With increased survivorship, the long-term effects of cancer treatment are an important consideration for clinicians and patients. We reviewed the current literature on predicting trastuzumab-related cardiotoxicity and tested a clinical risk score (CRS) in a real-world breast cancer population to assess its utility in predicting permanent cardiotoxicity. Methods: In this retrospective exploratory cohort study of breast cancer patients referred to a cardio-oncology clinic at a tertiary care centre between October 2008 and August 2014, a CRS was calculated for each patient, and a sensitivity analysis was performed. Results: Of the 143 patients included in the study, 62 (43%) experienced a cardiac event, and of those 62 patients, 43 (69%) experienced full recovery of cardiac function. In applying the CRS, 119 patients (83%) would be considered at low risk, 14 (10%) at moderate risk, and 10 (7%) at high risk to develop heart failure or cardiomyopathy. When applied to the study population, the high-risk cut-off score had a sensitivity of 0.13 [95% confidence interval (CI): 0.08 to 0.20] and a specificity of 0.94 (95% CI: 0.87 to 0.97). The positive predictive value was 0.07 (95% CI: 0.03 to 0.13), and the negative predictive value was 0.93 (95% CI: 0.87 to 0.96). Conclusions: The CRS demonstrated good specificity and negative predictive value for the development of permanent cardiotoxicity in a real-world population of breast cancer patients, suggesting that intensive cardiac monitoring might not be warranted in low-risk patients, but that high-risk patients might benefit from early referral to cardio-oncology for optimization. Further study using the CRS in a larger breast cancer population is warranted to identify patients at low risk of long-term trastuzumab-related cardiotoxicity.