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

• Published in: Breast cancer research and treatment Vol. 168; no. 1; pp. 159 - 168
• Main Authors: Pezo, Rossanna C., Chen, Tom W., Berman, Hal K., Mulligan, Anna M., Razak, Albiruni A., Siu, Lillian L., Cescon, David W., Amir, Eitan, Elser, Christine, Warr, David G., Sridhar, Srikala S., Yu, Celeste, Wang, Lisa, Stockley, Tracy L., Kamel-Reid, Suzanne, Bedard, Philippe L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-02-2018; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - genetics; Breast - pathology; Breast - surgery; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer genetics; Cancer metastasis; Cancer research; Clinical outcomes; Clinical Trial; Clinical trials; Clinical Trials as Topic; DNA fingerprinting; DNA Mutational Analysis - methods; Female; Genetic aspects; Genetic research; Genomics - methods; Genotyping; Genotyping Techniques - methods; High-Throughput Nucleotide Sequencing; Humans; Mastectomy; Medical research; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Mutation; Oncology; p53 Protein; Prospective Studies; PTEN Phosphohydrolase - genetics; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Survival Analysis; Tumor proteins; Young Adult; Targeted therapies; mutation; Metastatic breast cancer; Molecular profiling; PIK3CA mutation
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-017-4580-2

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.