Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58, ZhongShan Er Lu, Guangzhou, Guangdong, 510080, P.R. China
Human epidermal growth factor receptor (HER2) negative metastatic breast cancer (BC) accounts for 73% of BC. The molecular analysis of this disease is essential for potential options for targeted therapy. Several promising clinical strategies are being evaluated which includes endocrine therapy, modified chemotherapy, angiogenesis inhibitors, immune checkpoint inhibitors, and anti-androgens. New therapeutic approaches are being developed that target BC patients with germline mutations in either BRCA1, BRCA2 as well as BRCAness, a condition in which tumors have molecular similarity to BRCA-mutated tumors. Poly (ADP-ribose) polymerase inhibitors (PARPi) which are effective therapy in germline BRCA1 and BRCA2 mutations, are also observed to be effective in somatic mutations. Germline mutations in the homologous recombination pathway genes could also contribute to PARPi sensitivity. PARPi act as chemo- and radio-sensitizers by limiting the DNA-damage response and potentiating the activity of chemo- and radio-therapy when used alone or in combination with chemotherapy. Apart from PARPi as monotherapy, additional researches are ongoing in combination with cytotoxic chemotherapeutics and targeted agents in HER2 negative BC. This review aims at the most recent developments in the targeted therapy, summarizes the recent clinical trials outcomes, along with the overview of ongoing clinical trials in HER2 negative patients with BRCA1/2 mutations and sporadic tumors with BRCAness.
Keywords: Her2 negative breast cancer, PARP inhibitors, BRCA, BRCAness, targeted therapy