作者: Jennifer J. Wheler , Barbara A. Parker , Jack Lee , Roman Yelensky , Stacy Moulder
DOI: 10.1158/1535-7163.TARG-13-A212
关键词: Targeted therapy 、 Internal medicine 、 PTEN 、 CDH1 、 Exact test 、 Progressive disease 、 Hormone therapy 、 Breast cancer 、 Metastatic breast cancer 、 Medicine 、 Oncology 、 Bioinformatics
摘要: Background: Next generation sequencing (NGS) has revealed significant heterogeneity among patients’ tumors. Molecular aberrations may be both prognostic and predictive. Methods: We retrospectively analyzed 57 patients with advanced or metastatic breast cancer, NGS profiling of their tumors, treated on Phase I trials at MD Anderson Cancer Center UCSD-Moores Center. The objectives this study were to: 1) characterize molecular and, 2) correlate response to targeted therapies. Results: Fifty-seven cancer tumors included. Fifty-six (98%) analysis demonstrated least one aberration. A total 216 somatic in 71 different genes identified including variants the same gene. There 99 mutations, 97 amplifications, 11 deletions, 5 splices, 2 truncations, 1 fusion rearrangement. most commonly mutated were: TP53 (26 patients, 46%); PIK3CA (18 32%); PIK3R1, GATA3 (5 9% each); BRCA2, CDH1, NF1 (3 5% each). common amplifications occurred at: CCND1, MYC (12 21% HER2 (official gene name ERBB2), MCL1 (7 12% FGFR1 (6 11%). In addition, PTEN deletion CDKN2 found 6 (11%) 3 (5%) respectively. Among those highest number included: variants); GATA PIK3R1 (4 BRCA variants). No two spectrum aberrations. Forty-four evaluable for therapies excluding single-agent hormone therapy (13 did not receive therapy). Thirty-seven received that either directly indirectly matched resulting complete responses (CR), partial (PR), 10 stable disease ≥ months (SD) 20 progressive (PD). Seven who SD patients) PD (Fisher9s exact test, p=0.88). Conclusion: Unique profiles genomic demonstrated. Further evaluation larger patient cohorts is warranted studies prospectively match Citation Information: Mol Ther 2013;12(11 Suppl):A212. Format: Jennifer J. Wheler, Barbara A. Parker, Jack Lee, Roman Yelensky, Stacy Moulder, Apostolia M. Tsimberidou, Filip Janku, Johnique T. Atkins, Ralph Zinner, Richard Q. Schwab, Maria Schwaederle, Vivek Subbiah, Siqing Fu, Philip Stephens, Razelle Kurzrock. cancer: Identification unique correlation response. [abstract]. In: Proceedings AACR-NCI-EORTC International Conference: Targets Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Suppl):Abstract nr A212.