An exploratory analysis of cardiac biomarkers in women receiving trastuzumab

Abstract

20557 Background: Trastuzumab induced cardiotoxicity may warrant discontinuation of therapy in up to 19% of women with early stage breast cancer, and is measured through assessment of left ventricular ejection fraction (LVEF). Previous studies have shown that elevated serum troponin I levels (Trop I - a cardiomyocyte structural protein) predict anthracycline-induced cardiac dysfunction prior to a decrease in LVEF. N-terminal pro-B type natriuretic peptide (NT pro-BNP) is a marker of increased left ventricular wall tension that may detect trastuzumab-induced heart dysfunction. Methods: We performed a cross sectional study in women receiving trastuzumab for breast cancer. Patients were required to have a normal LVEF and no clinical signs of heart failure. Serum Trop I and NT pro-BNP were assayed immediately prior to trastuzumab infusion (t0; n=36) and 24 hours later (t24; n=31). Results: Patient characteristics were: mean age 52 (range 25–86); 30 (83%) anthracycline pre-treated; 23 (64%) early stage and 13 (36%) advanced disease; median duration of trastuzumab therapy 30 weeks (range 3–182). Trop I was not elevated (>0.20ng/mL) in any patient at 0 or 24 hours. 15/36 (42%) patients had at least one NT pro-BNP level above the upper limit of normal (ULN, defined as >95th centile amongst healthy volunteers) and both levels were above the ULN in 8/31 (26%) patients. There was no significant difference between NT pro-BNP levels taken at t0 and t24 (Table 1). Conclusion: NT pro-BNP levels are elevated in a significant proportion of patients with normal LVEF receiving trastuzumab. Trastuzumab does not induce an acute rise in NT pro-BNP levels at 24 hours. Troponin I levels are not raised in this group, perhaps reflecting the mechanism of cardiotoxicity. These data are exploratory and have informed the design and power calculations of a larger study examining the predictive utility of serial serum NT pro-BNP levels for trastuzumab-induced cardiotoxicity in the adjuvant setting. NT pro-BNP levels (pg/mL) Pre-infusion, t0 Post-infusion, t24 N 36 31 Mean 163.5 168.1 SEM 56.6 49.3 Median 86.4 74.6 Spearman’s correlation 0.844 Wilcoxon signed ranks p value 0.969 ULN : <75 yrs : 110 pg/mL; >75 yrs : 589 pg/mL No significant financial relationships to disclose.