Next generation sequencing demonstrates multiple gene amplifications and mutations in 3 patients with estrogen receptor positive breast cancer with responses to treatment with …

Background:Gene amplifications in breast cancer may indicate poor prognosis disease, particularly for patients with multiple amplifications. Endocrine response and resistance in breast cancer maybe revealed to PI3K/AKT/mTOR pathway activation.Patients and Methods:We analyzed tissue with next generation sequencing (NGS) from 3 patients with estrogen receptor (ER)-positive breast cancer treated on a dose escalation study with anastrozole, an aromatase inhibitor, and everolimus, an mTOR inhibitor. Genomic libraries were captured for 3230 exons in 182 cancer related genes plus 37 introns from 14 genes, often rearranged in cancer (Foundation Medicine, Cambridge, MA).Results:Twelve of 50 evaluable patients with ER-positive breast and gynecologic tumors treated with anastrozole (1mg PO daily) and everolimus (either 5mg PO daily or 10mg PO daily) had SD ≥ 6 months/PR/CR. NGS analysis on 3 of …