Risk Stratification for Trastuzumab-Induced Cardiac Dysfunction and Potential Implications for Surveillance

Although patient factors and sequential anthracycline use contribute to risk for cancer therapy-related cardiac dysfunction (CTRCD) with HER2-directed cancer therapy, frequent (every 3 months) left ventricular ejection fraction (LVEF) surveillance is recommended irrespective of baseline risk.

The aim of this study was to examine the incidence of trastuzumab-associated CTRCD in a contemporary cohort with HER2-positive breast cancer and assess the performance of a risk assessment tool to identify patients at low risk for CTRCD to guide risk-based surveillance strategies.

A retrospective cohort of patients with HER2-positive breast cancer treated with trastuzumab at a tertiary cancer center was examined. Patients were categorized as low, medium, and high or very high risk for CTRCD by Heart Failure Association/International Cardio-Oncology Society risk assessment.

Of 496 patients treated with trastuzumab, 29.8% also received anthracyclines. Over a median follow-up period of 51 months, 8.7% developed CTRCD, but only 1.6% had associated heart failure (HF). CTRCD rates were 3.6%, 12.8%, and 32.1% in low-risk, medium-risk, and high or very high risk groups, respectively. HF incidence was 0.4% in the low-risk group and 2.1% in the medium-risk group, with no HF in patients at low- or medium-risk who received trastuzumab without anthracyclines. HF was observed in 11% of high-risk patients. The risk assessment had a negative predictive value for CTRCD in low vs moderate- or high-risk patients of 96.4% (95% CI: 93.5%-98.3%).

The findings support the exploration of a prospective personalized risk-based approach to cardiac LVEF surveillance during trastuzumab therapy. Less frequent LVEF monitoring in low-risk patients may optimize resource use and reduce patient burden without compromising safety.