Homologous Repair Deficiency Status and Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: The Best Current Biomarker to Select the Most Appropriate Treatment?

Author(s): Giovanna Garufi, Armando Orlandi, Antonella Palazzo, Giampaolo Tortora, Emilio Bria, Luisa Carbognin

Despite recent discoveries regarding the genomic characterization of triple-negative breast cancer (TNBC), the neoadjuvant treatment of TNBC is focused on the anthracycline- and taxane- (AT) based chemotherapy regimens. Clinical studies have highlighted the role of platinum in the neoadjuvant setting, because its addition to AT-based neoadjuvant chemotherapy (NACT) increases the rate of pathological complete response (pCR). Retrospective analysis showed that the pCR rate is not influenced by the BRCA mutational status in relation to platinum use, while promising data found homologous repair deficiency (HRD) status as a potential predictive factor of response to platinum based neoadjuvant treatment. We will look specifically at the role of HRD status in platinum response prediction for two reasons: first, to understand whether the anthracycline use can be avoided in some TNBC subpopulations, sparing toxicity; second, to understand if it is possible, through the modulation of known oncogenic pathways, to make a TNBC from HRD-low to HRD-high phenotype and to exploit its sensitivity to DNA-damaging agents.