Genomic and Epigenomic BRCA Alterations Predict Adaptive Resistance and Response to Platinum-Based Therapy in Patients With Triple-Negative Breast and Ovarian Carcinomas

Loss of BRCA1 or BRCA2 activity is common in TNBC and ovarian cancer; however, the type of alteration can result in different treatment responses. Here, Menghi et al. examined the differences in response to platinum therapy of patients with TNBC and ovarian cancer who had BRCA loss or genetic alterations as compared to promotor methylation of BRCA. They saw that both patients and mice with promotor methylation were able to adaptively lose methylation, gain BRCA1 expression, and acquire resistance to platinum therapy.