Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial

Abstract

mutations in <i>BRCA1/2</i> were detected in seven (13.5%) patients, while alterations in other HRR genes or hypermethylation in <i>BRCA1</i> or <i>RAD51C</i> were reported in 16 (30.7%) patients; furthermore, no alteration was found in the majority of patients (<i>n</i> = 29; 55.8%). Among 27 patients who received platinum-based chemotherapy, the disease control rate was 80%, 55% and 18% (groups A, B and C, respectively; <i>p</i> = 0.049). Regarding group B, patients with disease control exhibited mutations in <i>FANCL</i>, <i>FANCA</i> and the <i>RAD51D</i> genes or <i>RAD51C</i> methylation; Conclusion: mutations in HRR genes and epimutations in <i>RAD51C</i> were associated with disease control through platinum-based chemotherapy. As such, apart from well-characterized alterations in <i>BRCA1/2</i>, a more comprehensive evaluation of HRD should be considered in order to enlarge the selection of patients with mTNBC that could benefit from platinum-based chemotherapy.