Abstract P5-06-08: BRCA1 promoter hypermethylation, but not BRCA1 expression, is associated with basal-like features and good prognosis in triple negative breast cancer

Abstract

Abstract Purpose: BRCA1 gene mutation is closely associated with familial hereditary breast cancer. Decreased expression of BRCA1 could be detected in certain types of sporadic breast cancer without BRCA1 mutations. Aberrant hypermethylation of DNA promoter CpG islands is one of the mechanisms by which tumor suppressor gene expression and function could be lost. We investigated BRCA1 methylation status and BRCA1 immunohistochemistry (IHC) expression and their clinic-pathological significance in triple negative breast cancers (TNBC). Patients and methods: We analyzed BRCA1 promoter hypermethylation using a methylation specific PCR assay and BRCA1 IHC expression using the MS110 monoclonal antibody and Garg and Meisel scoring classification. Their clinicopathological and prognostic implications were analyzed in a TMA of TNBC samples from European patients. Results: To date, 123 TNBC have been analyzed. 25 tumors (20%) presented a BRCA1 promoter hypermethylation. BRCA1 IHC expression was retained, equivocal and lost in 73 (59%), 17 (14%) and 33 (27%) cases respectively. No significant correlation was found between promoter hypermethylation and protein expression (p=0.28). A significant association was found between promoter hypermethylation and basal staining (CK5/6 and/or EGFR IHC staining), while using either a 10% or 1% cut-off for basal definition (p= 0.04 and 0.03, respectively). No significant association was found between BRCA1 expression and a basal phenotype. With a median follow-up of 6.3 years (range [0.01 – 11.8]), 35 relapses and deaths occurred (71.2% 5-years RFS and 77.8 5-years OS). RFS was significantly associated with T and N stage, and a trend was seen for a better prognosis of BRCA1 promoter hypermethylated tumors (5-years RFS: 84% vs. 68%, p=0.07). OS was significantly associated with T and N stage, and adjuvant chemotherapy. Conclusion: BRCA1 promoter hypermethylation is associated with basal-like features and seems to be associated with a better prognosis in TNBC. BRCA1 IHC expression is not a good surrogate marker for evaluation of the methylation status of the tumors, and did not appear associated with prognosis in our series. The data will be updated for the meeting in term of number of analyzed tumors in order to strengthen the statistical analysis. Citation Format: Jacot W, Simony-Lafontaine J, Mollevi C, Boissierre F, Lopez-Crapez E, Chartron E, Lamy P-J, Guiu S. BRCA1 promoter hypermethylation, but not BRCA1 expression, is associated with basal-like features and good prognosis in triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-06-08.