Using Novel Biomarkers to Predict Chemo-Induced Cardiovascular Toxicity in Patients with Breast Cancer

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 have been inconsistent. Recently, the 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. 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. 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. 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. 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.