Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

摘要

Treatment of triple negative breast cancer (TNBC) has been a big challenge since it is defined. To date, platinum-based chemotherapy has played a significant role in the treatment of TNBC patients. However, some patients do not respond to platinum salts or gradually develop chemoresistance, resulting in little effect, or even some adverse effects. Here, we review numerous preclinical and clinical investigations to summarize possible mechanisms and potential predictive biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD) resulting from the loss of BRCA function is the main rationale of platinum efficacy in TNBC. BRCA mutation and methylation have been demonstrated to be important potential biomarkers. Based on genome-wide effects, BRCA-like classifier can identify the functional loss of BRCA and work as the predictor. HRD score that is able to identify the BRCAness and predict the sensitivity of platinum is increasingly considered. Taken together, all findings suggest that HR deficiency profile encompassed by BRCA mutation and high HRD score could predict response to platinum, even to other DNA-damage inducing agents. p53 family members and molecular subtypes of TNBC are also important alternative considerations for predicting platinum response based on the preclinical trials. Currently, tumor infiltrating lymphocyte level and thrombocytopenia are emerging as predictive biomarkers.