A serum biomarker panel for early detection of treatment-related cardiotoxicity in early HER2-positive breast cancer patients

Background: Standard treatment for human epidermal growth factor 2 positive (HER2+) breast cancer poses a high risk of cardiotoxicity, however, it still lacks predictive biomarkers. This study assesses five candidate biomarkers for early treatment-related cardiotoxicity prediction. Methods: All enrolled patients received the full treatment protocol consisting of anthracycline followed by 12 months of trastuzumab alone or with pertuzumab. Patients were prospectively followed for 27 months. Measurements of high-sensitivity troponin I (hs-Tn I), high-sensitivity C reactive protein (hs-CRP), N-terminal pro b-type natriuretic peptide, interleukin-6, and uric acid were performed at baseline, after anthracyclines, and after four cycles of anti-HER2 agents. Left ventricular ejection fraction (LVEF) measurements and full cardiac examination were performed every 3 months from baseline point until study end. Cardiotoxicity was defined as either an absolute decrease in LVEF of ≥15% or a drop in LVEF of ≥10% from the baseline to <50%. Results: Among 44 patients, cardiotoxicity occurred in 11 patients (25%). Higher risk of cardiotoxicity was associated with hs-Tn I levels ≥82 ng/L measured after four cycles of anti-HER2 agents. Elevated hs-CRP values ≥2.8 mg/L after 4 cycles of anthracyclines were also associated with increased risk. The highest risk was observed when both elevated hs-Tn I (≥82 ng/L after four cycles of anti-HER2 agents) and elevated hs-CRP (after four cycles of anthracyclines) were present. Conclusion: The interaction between both hs-Tn I and hs-CRP demonstrates significant predictive value for cardiotoxicity risk related to HER2+ breast cancer treatment.