An In-Vivo Investigation of the Cardio-Protective Potential of Aspirin, β-oestradiol and Calcipotriol for Trastuzumab Treatment of Her-2 Positive Breast Cancer

Abstract

The 15-25% of breast cancers that overexpress human epidermal growth factor receptor type 2 (Her-2) are aggressive and more difficult to treat with conventional chemotherapy than their oestrogen receptor positive (ER+) counterparts. Adjuvant trastuzumab, a specific Her-2 targeting monoclonal antibody, has significantly improved the prognosis of women with metastatic and early Her-2 positive breast cancer. Yet clinically relevant cardio-toxicity continues to undermine its gains. This study investigated the unexplored potential of aspirin, β-oestradiol and calcipotriol to attenuate the antibody’s cardio-toxicity in an adult female Balb/c mouse model using serial echocardiography to assess left ventricular function at baseline and after treatment. Mean changes in left ventricular function were compared within and between treatment groups. Trastuzumab demonstrated statistically significant left ventricular dysfunction, detectable by reductions in speckle tracking echocardiographic parameters (global radial strain) from baseline. Calcipotriol did not abrogate these cardio-toxic effects. Conversely, β-oestradiol, high and low dose aspirin attenuated these early and subtle signs of trastuzumab-induced cardiac dysfunction. The findings of this pilot study suggest that β-oestradiol or aspirin may provide cardio-protection against trastuzumab in-vivo, and larger definitive studies are justified.