Homologous recombination deficiency in breast cancer

SummaryBRCA mutation-related DNA repair deficiencies increase the individual sensitivity to DNA-targeting agents. Therefore, the patient ’sBRCA mutational status is evaluated in clinical practice as a  predictive marker in response to platinum salts and poly-ADP-ribose polymerase (PARP) inhibitors for breast cancer treatment. A substantial subset ofBRCAwild-type breast cancer lesions, however, share both prominent molecular characteristics and clinical behavior patterns with cancer that harborsBRCA mutations, including DNA repair deficiencies. Also referred to as “BRCAness”, this observation is related to aberrations of the homologous recombination (HR) repair pathway, which deprive cancer cells of the ability to adequately mend potentially lethal double-strand breaks and result in a BRCA-like genomic instability. Hence, HR deficiency is a  promising target for related therapeutic options and the predictive potential of HR testing for treatment response has been increasingly studied. Several HR deficiency-testing assays have been proposed and prospectively validated for various cancer types; however, preliminary results in early brea st cancer are inconsistent. As scientific evidence for a potential therapeutic benefit in breast cancer is scarce, HR testing remains highly experimental and should be limited to the boundaries of clinical studies until results of ongoing phase 3 trials are available.

Source: Memo - Magazine of European Medical Oncology - June 8, 2020 Category: Cancer & Oncology Source Type: research