Association of BRCAl-related DNA repair genetic variations and high incidence of metastasis in triple-negative breast cancer
- VernacularTitle:BRCA 1基因相关的DNA修复通路异常与三阴乳腺癌化疗药物选择的关系
- Author:
Ning WANG
;
Yajie WANG
- Publication Type:Journal Article
- Keywords:
BRCA 1;
DNA damage repair;
triple-negative breast cancer;
metastasis
- From:China Oncology
2009;19(7):552-556
- CountryChina
- Language:Chinese
-
Abstract:
Triple-negative breast cancer is defined by the absence of expression of oestrogen, progesterone, and Her-2 receptors. The clinicopathological characteristics include: higher histological grades, earlier relapse with worse prognosis, and a higher incidence of visceral metastases than bone metastases. Since it has no response to hormone treatment and targeted therapy for Her-2, chemotherapy became the main therapy. In addition, it may have a relationship with basal-like breast cancer and BRCAl-related breast cancer on the phenotype and molecular level. Inter-individual variations in DNA damage and repair have been associated with an increased risk of breast cancer. BRCA1 together with its associated genes such as BRCA2, ATM, RAD51 and CHEK2 play vital roles in different DNA repair pathways to preserve genome stability. Therefore variations of BRCA1 and its associated genes in multiple repair pathways may result in reduced DNA repair capacity and altered sensitivity to cytotoxic chemotherapeutic agents,which could promote incidence of distant metastases. Reduced DNA repair capacity and dysfunctional BRCA1 pathway in triple-negative breast cancer have been reported, however the detailed mechanisms are still unknown. Do the genetic variations of tumor cells or resistance of tumor cells to therapeutic drugs play the dominant role in high incidence of metastases in patients with triple-negative breast cancer? In this review, the association of dysfunctional BRCA1-related DNA repair pathways with high incidence of metastasis in triple-negative breast cancer would be introduced.
