Abstract P2-03-02: Differential mutation pattern between neoadjuvant and metastatic settings in breast cancer patients

Abstract

Background: Dysregulated signaling pathways occur in human cancers including breast cancer, making it a rational target for novel genome guided combinatorial personalized therapies. The aim of the present study was to investigate the different genetic mutation pattern between neoadjuvant and metastatic settings in breast cancer patients to guide research and clinical treatment. Material and Methods: 150 breast cancer patients were involved in this study. 38 patients were receiving neoadjuvant treatment and 112 patients were in the metastatic setting. Tumor specimens obtained from the 150 patients were subjected to genetic mutation testing by FoundationOne. Genetic alterations detected by FoundationOne test were collected and analyzed. Results: 96 and 149 different genes where reported by FoundationOne in neoadjuvant and metastatic setting respectively. The average number of non-synonymous mutation was five per case in the neoadjuvant setting and six per case in the metastatic setting. TP53 (58%), MYC (32%), PIK3CA (29%), PTEN (16%), CDH1 (13%), CCND1 (11%), EMSY (11%), LYN (11%) and ZNF703 (11%) were the most seen mutations in neoadjuvant setting. TP53 (40%), PIK3CA (39%), MYC (22%), CCND1 (21%), FGF19 (21%), FGF4 (21%), CDH1 (20%), FGF3 (19%), ERBB2 (17%), ESR1 (14%), FGFR1 (14%), ZNF703 (14%), GATA3 (13%), MYST3 (11%), PTEN (11%), EMSY (10%), NF1 (10%) and ZNF217 (10%) were the most seen mutations in metastatic setting. ESR1 and GATA3, which are seen in 14% and 13% of metastatic breast cancer patients, were not reported in neoadjuvant breast patients. Moreover, among the 16 metastatic breast cancer patients who has ESR1 mutation, 9 (56%) of them presented with PIK3CA or other genetic mutations which are directly involved in the phosphoinositide 3-kinase (PI3K)/AKT pathway. Conclusion: A significantly more mutation in Receptor Tyrosine Kinases (RTKs)/ Growth Factor Signaling ( especially ERBB and FGFR pathways) was reported in the metastatic setting compare to the neoadjuvant setting, suggesting a critical role of the RTKs in metastatic breast cancer patients. The coexisting of ESR1 and PI3K/AKT pathway alteration and the absence of ESR1 in neoadjuvant setting also suggested that in early stage breast cancer patients who have a PI3K pathway alterations; there is a higher chance to develop ESR1 mutation with disease progression. Citation Format: Xu B, Williams C, De P, Dey N, Klein J, Williams K, McMillan A, Leyland-Jones B. Differential mutation pattern between neoadjuvant and metastatic settings in breast cancer patients [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 P2-03-02.