Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

BRCA1 methylation in triple-negative breast cancer

Date

20 Dec 2015

Session

Poster presentation 2

Presenters

Asuka Kawachi

Citation

Annals of Oncology (2015) 26 (suppl_9): 16-33. 10.1093/annonc/mdv519

Authors

A. Kawachi1, E. Okochi-Takada2, T. Shimoi3, A. Shimomura3, M. Kodaira1, M. Yunokawa4, K. Yonemori3, C. Shimizu1, Y. Fujiwara1, T. Ushijima2, K. Tamura1

Author affiliations

  • 1 Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2 Epigenomics, National Cancer Center Research Institute, Tokyo/JP
  • 3 Breast And Medical Oncology, National Cancer Center Hospital, Tokyo/JP
  • 4 Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
More

Resources

Aim/Background

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.

Methods

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.

Results

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).

Conclusions

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.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings