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Clinical outcomes based on multigene profiling in metastatic breast cancer patients
- Source :
- Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 2016.
-
Abstract
- // Reva K. Basho 1,* , Debora de Melo Gagliato 2,* , Naoto T. Ueno 2 , Chetna Wathoo 3 , Huiqin Chen 4 , Maryam Shariati 5 , Caimiao Wei 4,6 , Ricardo H. Alvarez 2,7 , Stacy L. Moulder 2 , Aysegul A. Sahin 8 , Sinchita Roy-Chowdhuri 8 , Mariana Chavez-MacGregor 2,9 , Jennifer K. Litton 2 , Vincent Valero 2 , Raja Luthra 8 , Jia Zeng 3 , Kenna R. Shaw 3 , John Mendelsohn 3,10 , Gordon B. Mills 3,11 , Debu Tripathy 2 and Funda Meric-Bernstam 3,5,12 1 Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Investigational Cancer Therapeutics (Phase I Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Pfizer, Inc, New York, NY, USA 7 The Cancer Treatment Centers of America, Chicago, IL, USA 8 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 9 Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 10 Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 11 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 12 Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors have contributed equally to this work Correspondence to: Funda Meric-Bernstam, email: // Keywords : metastatic breast cancer, genomics, TP53, PIK3CA Received : April 06, 2016 Accepted : October 13, 2016 Published : October 28, 2016 Abstract BACKGROUND: Identifying the clinical impact of recurrent mutations can help define their role in cancer. Here, we identify frequent hotspot mutations in metastatic breast cancer (MBC) patients and associate them with clinical outcomes. PATIENTS AND METHODS: Hotspot mutation testing was conducted in 500 MBC patients using an 11 gene ( N = 126) and/or 46 or 50 gene ( N = 391) panel. Patients were stratified by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status. Clinical outcomes were retrospectively collected. RESULTS: Hotspot mutations were most frequently detected in TP53 (30%), PIK3CA (27%) and AKT1 (4%). Triple-negative breast cancer (TNBC) patients had the highest incidence of TP53 (58%) and the lowest incidence of PIK3CA (9%) mutations. TP53 mutation was associated with shorter relapse-free survival (RFS) (median 22 vs 42months; P < 0.001) and overall survival (OS) from diagnosis of distant metastatic disease (median 26 vs 51months; P < 0.001). Conversely, PIK3CA mutation was associated with a trend towards better clinical outcomes including RFS (median 41 vs 30months; P = 0.074) and OS (52 vs 40months; P = 0.066). In HR-positive patients, TP53 mutation was again associated with shorter RFS (median 30 vs 46months; P = 0.017) and OS (median 30 vs 55months; P = 0.001). When multivariable analysis was performed for RFS and OS, TP53 but not PIK3CA mutation remained a significant predictor of outcomes in the overall cohort and in HR-positive patients. CONCLUSIONS: Clinical hotspot sequencing identifies potentially actionable mutations. In this cohort, TP53 mutation was associated with worse clinical outcomes, while PIK3CA mutation did not remain a significant predictor of outcomes after multivariable analysis.
- Subjects :
- 0301 basic medicine
Gerontology
Oncology
medicine.medical_specialty
Genotype
Cancer therapy
Breast Neoplasms
Tp53 mutation
03 medical and health sciences
0302 clinical medicine
Breast cancer
Gene Frequency
Cancer Medicine
Surgical oncology
Internal medicine
Biomarkers, Tumor
medicine
Humans
Genomic medicine
Genetic Predisposition to Disease
TP53
Neoplasm Metastasis
neoplasms
Alleles
Neoplasm Staging
business.industry
Gene Expression Profiling
Genomics
PIK3CA
Prognosis
medicine.disease
Metastatic breast cancer
3. Good health
030104 developmental biology
Multigene Family
030220 oncology & carcinogenesis
Mutation
Cohort
Female
metastatic breast cancer
business
Priority Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....29cba23f9f0239501afdfe5b581e57bc