Using novel biomarkers to predict chemotherapy-induced cardiovascular toxicity in patients with breast cancer.

Abstract

e13002 Background: Despite improvement in survival in breast cancer patients from advanced therapies, rates of chemotherapy-induced cardiotoxicity manifesting as a decline in left ventricular ejection fraction (LVEF) have offset some of these benefits in patients receiving anthracycline-based chemotherapy followed by trastuzumab. Results suggesting clinical biomarkers predict cardiotoxicity are inconsistent. Recently, expression of angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) has shown to play a role in breast tumor growth. We sought to evaluate whether the presence of ATR1 and ET1 in breast cancer tissue using immunohistochemistry (IHC) and qRT-PCR can predict chemotherapy-induced cardiotoxicity. Methods: We hypothesized that elevated expression of ATR1 and ET1 in tumor tissue is associated with chemotherapy-induced cardiotoxicity (LVEF < 50%) compared to tissue from controls. Preliminarily, 34 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were retrieved for analysis. IHC and qRT-PCR for expression of ATR1 and ET1 was performed on all specimens. Results: We found that ET1 expression was significantly increased in patients with an LVEF < 50%. In addition, we noted the lower the LVEF, the higher the ET1 expression (p = 0.03). We also found patients with a change in LVEF of greater than 10% had more ET1 expression compared to those without a change in LVEF (p = 0.05). We did not find a significant relationship between ATR1 and LVEF. Conclusions: Increased ET1 expression in breast tumor tissue may predict cardiotoxicity. Our findings may aid in future research using novel biomarkers to predict breast cancer patients at risk for developing chemotherapy-induced cardiotoxicity. In addition, targeted therapies to these biomarkers may potentially help prevent the development of cardiotoxicity.