Breast cancers associated with BRCA1 are frequently of a higher grade, steroid hormone receptor negative, and appear to have a higher proportion of atypical or typical medullary subtype.
Breast cancers in patients with BRCA1 germline mutations are more often negative for estrogen receptor, progesterone receptor, and HER-2, and are more likely to be positive for p53 protein compared with controls.
Breast cancer formation in BRCA1 mutation carriers is generally accompanied by loss of the wild-type allele, suggesting that BRCA1 protein may function as a tumor suppressor.
Breast cancer penetrances were 27% (95% CI 20-34%) at age 50 years and 39% (27-52%) at age 70 in BRCA1 carriers, and 26% (0.18-0.34%) at age 50 and 44% (29-58%) at age 70 in BRCA2 carriers, and ovarian cancer penetrances were 14% (7-22%) at age 50 and 43% (21-66%) at age 70 in BRCA1 carriers and 3% (0-7%) at age 50 and 15% (4-26%) at age 70 in BRCA2 carriers.
Breast cancer arising in BRCA-1 mutation carriers is often estrogen receptor (ER) negative, unlike breast cancer developing in BRCA-2 mutation carriers.
Breast cancer occurring in carriers of ATM variants is not associated with distinctive histopathological features and does not resemble the tumour phenotype commonly observed in BRCA1 mutation carriers.
Breast cancer-specific mortality was strongly associated with promoter methylation of p16 [HR and 95% CI: 3.53 (1.83-6.78)], whereas the associations with of BRCA1 and APC were less pronounced [HR and 95% CI: 1.81 (1.18-2.78) and 1.46 (0.98-2.17), respectively].
Breast cancers occurring in women with germline BRCA1 mutations tend to fall into the category of triple-negative or basal-like phenotypes, such as metaplastic carcinoma.
Breast cancer-associated gene 1 (BRCA1) protein plays important roles in DNA damage and repair, homologous recombination, cell-cycle regulation, and apoptosis.
Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry population-based cohort study.
Breast cancer research has yielded several important results including the strong susceptibility genes,BRCA1 and BRCA2 and more recently 19 genes and genetic loci that confer a more moderate risk.The pace of discovery is accelerating as genetic technology and computational methods improve.