Abstract P3-08-24: Mutational characterization of HER2-positive breast cancer

Abstract

Abstract Background: Studies of mutational analysis have been widely reported in various global series of breast cancer. However, in the era of different phenotypes of breast cancer, these analyses should be more specific in order to find differences in each phenotype that could predict response to treatment. Particularly HER2 positive is a special subtype with different connotations that make the analysis of its genotype very interesting. Methods: Cohorts of 47 consecutive samples of HER2 positive breast cancer, treated in our institution were analyzed. It was conducted a mutational study with NGS technique of the most common genes involved in breast cancer. Results: 10 patients were metastatic at diagnostic, 17 with negative estrogen receptor expression, the median value of Ki67 was 45 (20-95) and the median initial tumor size was 33.5 mm (18-111). Inmunohistochemical expression of HER2 was +3 in 31 tumors and +2 in 15 with a median ratio by FISH of 3,2 (1,18-8,3). We also analyzed the expression of HER by PCR of mRNA in 35 samples with a median expression of 2,49 (0,26-33,15). 38 patients underwent surgical excision of the tumor with a pathologic complete response observed in 19. We found a total of 38 significant mutations and the genes with more frequent mutations were MCPH1 (100%), HNF1 (98%), p53 (96%), somatic BRCA1 (62%), TSC1 (30%), PIK3CA (23%), ATM (21%), ALK (15%) and somatic BRCA2 (13%). Although the aim of the study was to find the most frequent mutations in this subtype, we have also analyzed possible correlations of those with pathological response or with more common variables, finding no significance in any of them. Conclusions: In our series, we found a high percentage of mutations in MCPH1, HNF1 and p53 genes with almost 100% of mutations in p53 that are also limited in a very specific area. Also interesting is the 62% of mutations found in BRCA1 and 13% in BRCA2 that could allow more specific treatments in this subgroup. Although the study did not have the power to assess the predictive factor of these mutations, it is very suggestive that in the 7 patients with BRCA mutations, 6 achieved a complete pathological response. Citation Format: Velasco Sánchez A, Gasol Cudos A, Morales S, Veas Rodriguez J, Serrate López A, Mele Olivé J, Canosa Morales C. Mutational characterization of HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-24.