A DNA Repair BRCA1 Estrogen Receptor and Targeted Therapy in Breast Cancer

作者：Ratanaphan Adisorn^*

来源：International Journal of Molecular Sciences, 2012, 13(11): 14898-14916.

DOI：10.3390/ijms131114898

• BRCA1
• estrogen receptor
• fulvestrant
• antiestrogen
• triple-negative breast cancer

BRCA1 is a key mediator of DNA repair pathways and participates in the maintenance of the genomic integrity of cells. The control of DNA damage repair mechanisms by BRCA1 is of great interest since molecular defects in this pathway may reflect a predictive value in terms of a cell's sensitivity to DNA damaging agents or anticancer drugs. BRCA1 has been found to exhibit a hormone-dependent pattern of expression in breast cells. Wild-type BRCA1 is required for the inhibition of the growth of breast tumor cells in response to the pure steroidal ER alpha antagonist fulvestrant. Also a loss of BRCA1-mediated transcriptional activation of ER alpha expression results in increased resistance to ER alpha antagonists. Platinum-based drugs, poly(ADP-ribose) polymerase (PARP) inhibitors, and their combination are currently included in chemotherapy regimens for breast cancer. Preclinical and clinical studies in a BRCA1-defective setting have recently indicated a rationale for the use of these compounds against hereditary breast cancers. Initial findings indicate that neoadjuvant use of cisplatin results in high rates of complete pathological response in patients with breast cancer who have BRCA1 mutations. Cisplatin produces a better response in triple-negative breast cancer (TNBC) than in non-TNBC diseases in both the neoadjuvant and adjuvant settings. This implies that TNBC cells may harbor a dysfunctional BRCA1 repair pathway.

• 出版日期2012-11