MiRNAs profile as a signature for cardiovascular disease in long-term breast cancer female survivors: a pilot study

Abstract

Abstract Background/Introduction Cardiovascular diseases (CVD) is a matter of immediate concern among long term breast cancer (BC) survivors. An early identification of those patients who are at higher risk of developing CVD is warranted to tailor prevention strategies and improve their quality of life. Purpose To identify whether a specific miRNA signature exists in breast cancer female survivors who develop CVD in a long term follow up. Methods We performed cross-sectional comparison of miRNA expression between female BC survivors (i.e. individual with a diagnosis of invasive ductal carcinoma who were free from cancer at 10-year follow up and without known CVD before BC diagnosis) with CVD (n=11) and without CVD (n=11) matched for age, BC grade, treatment received and traditional cardiovascular risk factors. CVD was defined as the incidence of established atherosclerotic cardio- or cerebro-vascular diseases (i.e., ischemic heart disease, carotid endarterectomy, stroke, heart failure), atrial fibrillation or venous thromboembolism. Thirteen miRNAs were selected since they were involved in either BC and CVD. On plasma derived samples, miRNAs expression profile analysis was performed by retro-transcription and real-time PCR assays, using miRNA-specific probes. Results The BC female survivors (mean age 73 years, 70% hypertension, 60% histological grade 2 and 3) were treated with surgery. The majority (76%) received hormone therapy after surgery according to the BC receptor expression. In half of the cohort, radiotherapy was performed. Those female BC survivors developing CVD experienced more commonly cerebral or cardiovascular atherosclerotic events (70%). As reported in Figure 1, some miRNAs analyzed (miR-19a; miR-21; miR-24; miR-125b; miR-195) are upregulated in BC survivors who developed CVD. Of note miR-19a, miR-21 (and miR-195) increase is so significantly relevant to consider these miRNAs as candidate biomarkers. Conclusion(s) In this discovery cohort, a specific miRNA profile signature identified female BC survivors experiencing CVD. Validation of such signatures is needed in a larger cohort as well as mechanistic studies to understand what is the pathophysiological link between the miRNAs identified and vascular health. Nevertheless these miRNAs in both cancer and cardiac diseases are mainly associated with promotion of cell proliferation and inhibition of apoptotic processes. The clinical implications of using a specific miRNA profile as a likely early biomarker of adverse cardiovascular events are indeed of great interest to better preserve BC survivors' health.Figure 1