Abstract 15849: Early Increases in Biomarkers Predict Subsequent Cardiotoxicity in Breast Cancer Patients Treated With Doxorubicin, Taxanes, and Trastuzumab
Background: Current methods inadequately identify breast cancer patients at risk of cardiotoxicity with chemotherapy. We asked whether baseline levels, early changes, or biomarker combinations predict subsequent cardiotoxicity in breast cancer patients undergoing doxorubicin and trastuzumab therapy.
Methods: Her2+ breast cancer patients (n=78, median age 50) treated with anthracyclines followed by taxanes and trastuzumab were recruited from 4 centers in the US and Canada. Patients with an LVEF<50% prior to chemotherapy were excluded. Cardiotoxicity, as defined by the Cardiac Review and Evaluation Committee, was assessed over a maximum follow-up of 15 months. Eight biomarkers were measured at baseline and 3 months: high-sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), growth differentiation factor-15 (GDF-15), N-terminal-prohormone of brain natriuretic peptide (NT-proBNP), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), placental growth factor (PlGF), troponinI (TnI), and galectin-3 (gal-3). Changes in biomarker levels, and the association between cardiotoxicity and either baseline levels or changes in level were assessed.
Results: Levels of TnI, CRP, GDF-15, MPO, and galectin-3 increased significantly from baseline to 3 months (all p<0.05). Twenty-three patients experienced cardiotoxicity by 15 months. Interval changes in TnI (HR 1.38,95% CI 1.05-1.81,p=0.020) and MPO (HR 1.34,95% CI 1.00-1.80,p=0.048) were significantly associated with cardiotoxicity (Figure 1); in contrast, baseline levels were not. Jointly, the combination of TnI and MPO retained significance (p=0.007 and p=0.03, respectively), suggesting that the 2 biomarkers offer independent information about cardiotoxicity risk.
Conclusions: Our findings suggest that early interval changes in TnI and MPO may predict cardiotoxicity in breast cancer patients undergoing doxorubicin and trastuzumab therapy.
- © 2013 by American Heart Association, Inc.