Next-generation sequencing (NGS) in patients with advanced metastatic breast cancer: Identification of molecular alterations and analysis of associations with treatment on phase I studies at MD Anderson Cancer Center.

Abstract

1051 Background: Matching molecular alterations in patients with breast cancer to targeted therapy may increase response rates. Methods: We analyzed 22 sequential breast cancer patients with next generation sequencing (NGS) profiling of their tumors profiling (FoundationOne) treated on Phase I trials at the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. Objectives included: (1) characterize molecular alterations including mutations, amplifications and deletions, (2) evaluate associations between molecular alterations and response to therapy. Results: Twenty-two breast cancer patients, all female with median age 56 years were included. Twenty-one of 22 of patients (95%) analyzed demonstrated at least one molecular alteration. Twenty-one of 22 patients were evaluable for response to therapy (1 patient had not yet reached restaging). Sixteen patients were treated on Phase I trials with targeted therapy that was either directly or indirectly associated with a molecular alteration. Seven of these 16 patients (44%) achieved stable disease (SD) ≥6 months/partial response (PR)/complete response (CR) including 3 patients with PR and 1 patient with CR. Examples of molecular alterations include: mutations in PIK3CA (8 patients), PIK3R1 (2 patients), PTEN (1 patient), cMET (1 patient), NF1 (one patient); amplifications in CCND1 (8 patients), FGFR1 (4 patients), MYC (3 patients), MCL1 (3 patients), IRS2 (2 patients) and CCNE1(1 patient). Conclusions: A majority of patients with advanced or metastatic breast cancer whose tumors underwent NGS profiling demonstrated molecular alterations. Of the 9 patients who had either SD≥6 months/PR/CR on Phase I treatment, 7 (78%) had molecular alterations, either directly or indirectly associated with therapy. Further investigation of larger cohorts of patients with NGS is ongoing.