Abstract 5127: Incidence of molecular variants with and without Her-2-Neu expression and amplification in brain metastases of breast carcinoma and its prognostic significance.

Abstract

Background: Her-2-neu is one of the major genes and proteins, whose amplification and expression is widely used in modern medical practice in patients with breast carcinoma (BC). . This is a marker of poor prognosis and the "target" for Herceptin. The role of this marker in brain metastases is not very well investigated as it is in a primary tumor. Aim: To investigate the incidence of molecular variants of breast carcinoma in brain metastases (BM), to analyze Her-2-neu presence in them and evaluate its prognostic significance in patients with BMBC. Patients and methods: 90 FFPE tumor tissues and clinical data from consented patients with BMBC treated with surgery at the NN Burdenko Neurosurgery Institute (median age 52, age range 29-73 years) and 71 FFPE tumor tissues and clinical data from consented patients with primary BC without BM treated with surgery in AI Burnacyan Institute (median age 58, age range 28-80 years) have been obtained and evaluated. IHC staining of all 161 cases was performed with monoclonal antibodies to ER, PR, Ki-67and Her-2-neu (DAKO); Fluorescence in situ hybridization Her-2-neu LSI and CEP17 was also performed . Her-2 neu expression and amplification were estimated according to the standard ASCO recommendations. A special questionnaire was completed in order to obtain information about outcome of the patients. Statistical analysis was performed using the STATISTICA 8.0 software. Results: There were 5 molecular variants in BC and BMBC groups according to the ER, PR, Ki-67 and Her-2-Neu IHC expression and Her-2-Neu amplification. Their incidence among two groups were: luminal A - 42% vs. 9%, luminal B -10% vs. 3%, luminal Her-2-Neu positive - 14% vs. 27%, classical her-2-Neu positive -21% vs. 22%, and triple negative -13% vs. 27%, correspondingly. Patients in the BM group were in average 6 years younger than patients in ‘pure’ BC group. In BMBC group median time of BM's development among Her-2-Neu (amplified Her-2-neu gene) patients was significantly shorter than that among Her-2-neu -negative (without amplification) patients: 40 months (range 8-288) versus 84 months (range 24-131 (p<0,05). The general survival time from first signs of BM was 8 months (ranges 0-89) in Her-2-neu- positive patients versus 13 months (ranges 0-72) in Her-2-neu -negative patients. Conclusions: Despite the fact that luminal A variant of BC is the most common one among primary tumors, in patients with BMBC triple negative and luminal Her-2-neu variants occurred more frequently. As age analysis showed, patients from BMBC group were younger than patients without BM. Therefore we believe that ‘brain metastatic’ carcinomas occur in a much younger population. Patients with BMBC Her-2-neu amplification have more aggressive development of disease and shorter survival time, than without Her-2-neu amplification. Citation Format: Daniil Rotin, Oxana Paklina, NV Lobanova, GL Kobyakov, Olga Potapova. Incidence of molecular variants with and without Her-2-Neu expression and amplification in brain metastases of breast carcinoma and its prognostic significance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5127. doi:10.1158/1538-7445.AM2013-5127