Abstract 1697: Molecular features of refractory metastatic breast cancer

Background: Breast cancer is the most frequently diagnosed cancer in women worldwide and metastatic disease remains generally incurable, indicating a need for new drug discovery for metastatic breast cancer. In this study, we investigated the molecular features of refractory metastatic breast cancer. Methods: 74 metastatic refractory breast cancer patients who received molecular screening using next generation sequencing (NGS) between 2015 and 2017 were included in this analysis. Clinical and pathologic characteristics of these patients were reviewed. Results: Among the 74 patients, 27%, 51.4%, 10.8%, 10.8% had hormone receptor (HR)-negative HER2-negative, HR-positive HER2-negative, HR-positive HER2-positive, HR-negative HER2 positive. 54.1%, 48.6%, 9.5%, 47.3% had liver, lung, brain, bone metastasis. The most significantly mutated genes in refractory HR-positive breast tumors included TP53 (54.3%), PIK3CA (52.2%), CCND1 (19.6%) and ESR1 (15.2%). The most significantly mutated genes in refractory HR-negative breast tumors included TP53 (82.1%), PIK3CA (50%), MYC (14.3%), NF1 (14.3%) and KRAS (10.7%). Genes in PI3K/AKT/mTOR pathway were significantly mutated in 76.1% of HR-positive and 82.1% of HR-negative refractory breast tumors, respectively. Mutation of genes involved in DNA damage response pathway were observed in 23.9% of HR-positive tumors and 32.1% of HR-negative tumors. 21.7% of HR-positive tumors and only 3.6% of HR-negative tumors harbored at least one gene alteration in FGFR pathway (P = 0.04). 30.4% (17/74) of HR-positive tumors and 10.7% (3/28) of HR-negative tumors carried at least one gene alteration in CDK pathway (P = 0.50). 63.6% of tumors with alterations in FGFR pathway concurrently harbored alterations in CDK pathway. Alterations in FGFR or CDK pathway were significantly correlated with liver metastasis (P = 0.001). In addition, TP53 mutation was significantly correlated with brain metastasis (P = 0.022). Conclusions: These results provide a better understanding of molecular targets in refractory metastatic breast cancer which may lead to an improvement in the development of novel therapeutic strategies. Citation Format: Zhanhong Chen, Yuzi Zhang, Jing Zhao, Shangli Cai, Yongmei Yin. Molecular features of refractory metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 169