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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2018

Open Access 01-02-2018 | Clinical trial

Impact of multi-gene mutational profiling on clinical trial outcomes in metastatic breast cancer

Authors: Rossanna C. Pezo, Tom W. Chen, Hal K. Berman, Anna M. Mulligan, Albiruni A. Razak, Lillian L. Siu, David W. Cescon, Eitan Amir, Christine Elser, David G. Warr, Srikala S. Sridhar, Celeste Yu, Lisa Wang, Tracy L. Stockley, Suzanne Kamel-Reid, Philippe L. Bedard

Published in: Breast Cancer Research and Treatment | Issue 1/2018

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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 ≥ 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.
Appendix
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Metadata
Title
Impact of multi-gene mutational profiling on clinical trial outcomes in metastatic breast cancer
Authors
Rossanna C. Pezo
Tom W. Chen
Hal K. Berman
Anna M. Mulligan
Albiruni A. Razak
Lillian L. Siu
David W. Cescon
Eitan Amir
Christine Elser
David G. Warr
Srikala S. Sridhar
Celeste Yu
Lisa Wang
Tracy L. Stockley
Suzanne Kamel-Reid
Philippe L. Bedard
Publication date
01-02-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4580-2

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