Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity

Area of Science:

• Oncology
• Cardiology
• Pharmacology

Background:

• Trastuzumab is a crucial therapy for HER2-positive breast cancer.
• Trastuzumab-related cardiotoxicity (TRC) is a significant concern, impacting treatment efficacy and patient outcomes.
• Previous studies on TRC biomarkers have yielded inconsistent results due to population heterogeneity.

Purpose of the Study:

• To prospectively identify clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC).
• To develop a predictive model for TRC in patients receiving adjuvant trastuzumab therapy.
• To assess the role of LVEF, troponin T, and natriuretic peptide levels in predicting TRC.

Main Methods:

• Prospective recruitment of 222 early-stage HER2-positive breast cancer patients undergoing adjuvant anthracyclines and trastuzumab.
• Serial measurements of LVEF, troponin T, and NT-proBNP at baseline, post-anthracycline, and every 3 months during trastuzumab treatment.
• Analysis of germline polymorphisms in ERBB2, FCGR2A, and FCGR3A, with TRC defined by specific cardiac events or LVEF decline criteria.

Main Results:

• TRC occurred in 8.3% of patients.
• Lower baseline LVEF and a greater LVEF decline post-anthracycline were independently associated with TRC (ORs 3.9 and 7.9, respectively).
• Troponin T, NT-proBNP (on multivariate analysis), and genetic polymorphisms showed no significant association with TRC.

Conclusions:

• Baseline LVEF and post-anthracycline LVEF change are independent predictors of TRC.
• The identified predictors can be used to develop a "low-risk TRC score" for patient stratification.
• Further research may not require additional biomarkers beyond LVEF for TRC prediction.