Progress and prospects in research and clinical practice of hormone receptor-positive, HER-2-negative breast cancer with BRCA1/2 mutations

Abstract

Breast cancer (BC) is a heterogeneous disease that is the most common cancer in women worldwide. However, precise subtyping and corresponding treatments have improved patient outcomes. Hormone receptor (HR)-positive, human epidermal growth factor receptor type 2 (HER2)-negative (HR+/HER2-) BC with BRCA1 and/or BRCA2 mutations (BRCA1/2m) is a unique BC subset with dual drivers: homologous recombination deficiency and hormone receptor signaling. Wild-type BRCA1/2 suppresses estrogen receptor-mediated signaling. Loss-of-function mutations in BRCA1/2 release estrogen receptor suppression, leading to reduced sensitivity to endocrine therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) exert antitumor effects against this subtype and can be used in combination with endocrine therapy. Although PARPis have been evaluated in metastatic triple-negative breast cancer, their efficacy against HR+/HER2- BC has not been clearly established. The present review summarizes recent advances and prospects in the progress of the HR+/HER2-/BRCA1/2m subgroup. As such, this article provides theoretical guidance for future research and promotes the use of PARPis for the treatment of HR+/HER2-/BRCA1/2m BC.