학술논문

Impact of multi-gene mutational profiling on clinical trial outcomes in metastatic breast cancer
Document Type
Academic Journal
Source
Breast Cancer Research and Treatment. February, 2018, Vol. 168 Issue 1, p159, 10 p.
Subject
Clinical trials
Genetic research
Cancer genetics -- Genetic aspects
Tumor proteins -- Genetic aspects
Medical research
Breast cancer -- Genetic aspects
Cancer metastasis -- Genetic aspects
Language
English
ISSN
0167-6806
Abstract
Purpose Next-generation sequencing (NGS) has identified recurrent genomic alterations in metastatic breast cancer (MBC); however, the clinical utility of incorporating routine sequencing to guide treatment decisions in this setting is unclear. We examine the frequency of genomic alterations in MBC patients from academic and community hospitals and correlate with clinical outcomes. Methods MBC patients with good performance status were prospectively recruited at the Princess Margaret Cancer Centre (PM) in Canada. Molecular profiling on DNA extracted from FFPE archival tissues was performed on the Sequenom MassArray platform or the TruSeq Amplicon Cancer Panel (TSACP) on the MiSeq platform. Clinical trial outcomes by RECIST 1.1 and time on treatment were reviewed retrospectively. Results From January 2012 to November 2015, 483 MBC patients were enrolled and 440 were genotyped. At least one somatic mutation was identified in 46% of patients, most commonly in PIK3CA (28%) or TP53 (13%). Of 203 patients with [greater than or equal to] 1 mutation(s), 15% were treated on genotype-matched and 9% on non-matched trials. There was no significant difference for median time on treatment for patients treated on matched vs. non-matched therapies (3.6 vs. 3.8 months; p = 0.89). Conclusions This study provides real-world outcomes on hotspot genotyping and small targeted panel sequencing of MBC patients from academic and community settings. Few patients were matched to clinical trials with targeted therapies. More comprehensive profiling and improved access to clinical trials may increase therapeutic options for patients with actionable mutations. Further studies are needed to evaluate if this approach leads to improved clinical outcomes.
Author(s): Rossanna C. Pezo [sup.1] [sup.2] [sup.9] , Tom W. Chen [sup.3] , Hal K. Berman [sup.4] [sup.5] , Anna M. Mulligan [sup.4] [sup.5] , Albiruni A. Razak [sup.1] [sup.2] [...]