Functional inactivation of BRCA1 gene increase the risk of developing breast cancer. Germline mutation of BRCA1 is responsible for Hereditary Breast and Ovarian Cancer. BRCA1 promoter methylation has been proposed as an alternative mechanism to inactivate BRCA1 in sporadic breast cancer. Most of cases with BRCA1 mutations are triple negative breast cancer (TNBC) but, the association between each subtypes of breast cancer and BRCA1 methylation is not clear. Thus, we investigated the BRCA1 methylation status and protein expression of BRCA1 in each subtypes of breast cancer.
121 samples, which contained 82 frozen and 39 acetone embedded samples, were obtained from breast cancer patients undergoing surgery with informed consents. Using methylation-specific PCR analysis which was validated based on cell line survey, methylation levels were calculated as a percentage of the reference. Setting a cut-off value of 10%, positive methylation was determined. The association between BRCA methylation and clinicopatholgical factors was analyzed by Chi-square test.
The number of each subtypes is 43 in hormone receptor (HR) + , HER2-, 21 in HR + , HER2-, 19 in HR-, HER2 + , 38 in TNBC. Positive methylation was detected only in triple negative breast cancer (9/38, 24%) which is statistically significant compared with HR + , HER2- (0/43, p < 0.0.1), HR + , HER2 + (0/21, p < 0.05), and HR-, HER2- (0/19, p < 0.05). In cases with BRCA methylation, six out of eight cancer (75%) showed absence of BRCA protein. Frequency of low expression of BRCA protein by subtypes is; TNBCs (12/31, 39%), HR + , HER2- (2/41, 4.9%), HR + , HER2- (0/21, 0%), HR-, HER2+ (1/10, 10%) (p < 0.01).
Our data suggest hypermethylation of BRCA1 is highly related with TNBC subtype, which decrease BRCA protein expression. PARP inhibitors might be used as therapeutic targets for these population.
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All authors have declared no conflicts of interest.