The Framingham Risk Score Underestimates the Risk of Cardiovascular Events in the HER2-Positive Breast Cancer Population

Introduction: Patients with breast cancer (BCa) who overexpress HER2 (the human epidermal growth factor receptor 2) are at risk for cardiotoxicity when treated with anthracycline-based chemotherapy and HER2-targeted agents. The Framingham risk score (FRS) is a validated tool that stratifies patients into high-, intermediate-, or low-risk groups and calculates their 10-year risk of developing cardiovascular disease (CVD) based on past medical history, systolic blood pressure, and measurement of serum lipids. We retrospectively analyzed patients with HER2-positive BCa to determine whether the FRS predicts adverse cardiovascular (CV) events or cardiotoxicity in patients treated using anthracyclines or HER2-targeted therapy, or both. Methods: The FRS was determined for patients with BCa referred to The Ottawa Hospital Cardiology–Oncology Clinic from October 2008 to August 2014. The patients were stratified into high (≥20%), intermediate (10%–20%), and low (<10%) 10-year CV risk groups. Primary outcomes included CVD-related hospitalizations and deaths, and cardiotoxicity [drop in left ventricular ejection fraction (LVEF) of >10% to a LVEF ≤50%]. Results: Of the 152 patients included in the analysis (median follow-up: 40.7 months; range: 3.5–263 months), 47 (31%) were classified as high risk; 36 (24%), as intermediate risk; and 69 (45%), as low-risk. The number of CVD-related hospitalizations and deaths was 22, for an overall prevalence of 14%, with significantly more events occurring in high-risk than in low-risk patients (odds ratio: 4.18; 95% confidence limits: 1.47, 11.89). The FRS predicted a 10-year risk of any cv event of 11.2% and underestimated the actual rate of cv events in the entire cohort. High FRS was not associated with cardiotoxicity (p = 0.82). Conclusions: In a population of patients with HER2-positive BCa referred to a cardiology–oncology clinic, the FRS does not accurately predict the risk of cv events or cardiotoxicity.