Impact of multi-gene mutational profiling on clinical trial outcomes in metastatic breast cancer
Journal
Breast Cancer Research and Treatment
Journal Volume
168
Journal Issue
1
Pages
159-168
Date Issued
2018
Author(s)
Pezo R.C.
Berman H.K.
Mulligan A.M.
Razak A.A.
Siu L.L.
Cescon D.W.
Amir E.
Elser C.
Warr D.G.
Sridhar S.S.
Yu C.
Wang L.
Stockley T.L.
Kamel-Reid S.
Bedard P.L.
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. ? 2017, The Author(s).
Subjects
Metastatic breast cancer; Molecular profiling; PIK3CA mutation; Targeted therapies
SDGs
Other Subjects
epidermal growth factor receptor kinase inhibitor; phosphatidylinositol 3 kinase inhibitor; antineoplastic agent; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; PTEN protein, human; tumor marker; adult; aged; Article; clinical feature; female; gene mutation; genotyping technique; human; human tissue; major clinical study; metastatic breast cancer; molecular genetics; monotherapy; oncogene; PIK3CA gene; priority journal; prospective study; retrospective study; sequence analysis; somatic mutation; TP53 gene; breast; breast tumor; clinical trial (topic); dna mutational analysis; genetics; genomics; high throughput sequencing; mastectomy; middle aged; mortality; mutation; pathology; procedures; response evaluation criteria in solid tumors; surgery; survival analysis; very elderly; young adult; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Breast; Breast Neoplasms; Clinical Trials as Topic; DNA Mutational Analysis; Female; Genomics; Genotyping Techniques; High-Throughput Nucleotide Sequencing; Humans; Mastectomy; Middle Aged; Mutation; Prospective Studies; PTEN Phosphohydrolase; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Survival Analysis; Young Adult
Publisher
Springer New York LLC
Type
journal article