A New Genetic Risk Score to Predict the Outcome of Locally Advanced or Metastatic Breast Cancer Patients Treated With First-Line Exemestane: Results From a Prospective Study.
Adult
Aged
Aged, 80 and over
Androstadienes
/ therapeutic use
Antineoplastic Agents, Hormonal
/ therapeutic use
Aromatase Inhibitors
/ metabolism
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ drug therapy
DNA Repair
/ genetics
Female
Humans
Male
Middle Aged
Polymorphism, Genetic
Prospective Studies
Receptors, Estrogen
/ metabolism
Reproducibility of Results
Risk
Signal Transduction
/ genetics
Survival Analysis
Advanced breast cancer
Aromatase inhibitor
Hormone therapy
Polymorphisms
Survival
Journal
Clinical breast cancer
ISSN: 1938-0666
Titre abrégé: Clin Breast Cancer
Pays: United States
ID NLM: 100898731
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
01
10
2018
accepted:
18
11
2018
pubmed:
26
12
2018
medline:
15
4
2020
entrez:
26
12
2018
Statut:
ppublish
Résumé
Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival. Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility. Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively. In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management.
Identifiants
pubmed: 30584056
pii: S1526-8209(18)30679-7
doi: 10.1016/j.clbc.2018.11.009
pii:
doi:
Substances chimiques
Androstadienes
0
Antineoplastic Agents, Hormonal
0
Aromatase Inhibitors
0
Biomarkers, Tumor
0
Receptors, Estrogen
0
exemestane
NY22HMQ4BX
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
137-145.e4Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.