The Framingham risk score underestimates the risk of cardiovascular events in the HER2-positive breast cancer population

Abstract

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.

Keywords: Cardio-oncology; Framingham risk score; breast cancer; cardiotoxicity; her2; trastuzumab.

FIGURE 1

Patients with HER2-positive (HER2+) breast cancer (BCa) seen at the Cardiology–Oncology Clinic (COC) from October 2008 to August 2014 were stratified into low-, intermediate-, and high-risk groups based on high-risk features and the Framingham Risk Score (FRS). CV = cardiovascular; CVD = cardiovascular disease.

FIGURE 2

A Cox proportional hazards model of time to hospitalization or death attributable to cardiovascular (CV) disease for low- and intermediate-risk patients compared with high-risk patients showed a hazard ratio of 3.77 (95% confidence limits: 1.53, 9.35; p = 0.004). Compared with patients at low and intermediate risk, high-risk patients experienced severe CV events more quickly.