https://scholars.lib.ntu.edu.tw/handle/123456789/597550
標題: | Impact of multi-gene mutational profiling on clinical trial outcomes in metastatic breast cancer | 作者: | Pezo R.C. WEI-WU CHEN 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. |
關鍵字: | Metastatic breast cancer; Molecular profiling; PIK3CA mutation; Targeted therapies | 公開日期: | 2018 | 出版社: | Springer New York LLC | 卷: | 168 | 期: | 1 | 起(迄)頁: | 159-168 | 來源出版物: | Breast Cancer Research and Treatment | 摘要: | 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). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85035121738&doi=10.1007%2fs10549-017-4580-2&partnerID=40&md5=143ca5219d0b9e947275653718debc0c https://scholars.lib.ntu.edu.tw/handle/123456789/597550 |
ISSN: | 0167-6806 | DOI: | 10.1007/s10549-017-4580-2 | SDG/關鍵字: | 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 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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