Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review

Cancer-therapy related cardiotoxicity (CTRCT) is a significant and frequent complication of monoclonal antibody directed therapy, especially Trastuzumab, for human epidermal growth factor receptor 2 (HER2) overexpressing breast cancers. Reliable, clinically available molecular predictive markers of CTRCT have not yet been developed. Identifying specific genetic variants and their molecular markers, which make the host susceptible to this complication is key to personalised risk stratification. A systematic review was conducted until April 2021, using the Medline, Embase databases and Google Scholar, to identify studies genetic and RNA-related markers associated with CTRCT in HER2 positive breast cancer patients. So far, researchers have mainly focused on HER2 related polymorphisms, revealing codons 655 and 1170 variants as the most likely SNPs associated with cardiotoxicity, despite some contradictory results. More recently, new potential genetic markers unrelated to the HER2 gene, and linked to known cardiomyopathy genes or to genes regulating cardiomyocytes apoptosis and metabolism, have been detected. Moreover, microRNAs are gaining increasing recognition as additional potential molecular markers in the cardio-oncology field, supported by encouraging preliminary data about their relationship with cardiotoxicity in breast cancers. In this review, we sought to synthesize evidence for genetic variants and RNA-related molecular markers associated with cardiotoxicity in HER2-positive breast cancer.