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Polymorphic Variants in NR 1I3 and UGT 2B7 Predict Taxane Neurotoxicity and Have Prognostic Relevance in Patients With Breast Cancer: A Case‐Control Study
Author(s) -
Arbitrio Mariamena,
Scionti Francesca,
Altomare Emanuela,
Di Martino Maria Teresa,
Agapito Giuseppe,
Galeano Teresa,
Staropoli Nicoletta,
Iuliano Eleonora,
Grillone Francesco,
Fabiani Fernanda,
Caracciolo Daniele,
Cannataro Mario,
Arpino Grazia,
Santini Daniele,
Tassone Pierfrancesco,
Tagliaferri Pierosandro
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1391
Subject(s) - adme , taxane , pharmacology , breast cancer , medicine , chemistry , cancer , pharmacokinetics
Taxane‐related peripheral neuropathy (Tr PN ) is a dose‐limiting toxicity with important interindividual variability. Genetic polymorphisms in absorption, distribution, metabolism, and excretion ( ADME ) genes may account for variability in drug efficacy and/or toxicity. By the use of Affymetrix drug‐metabolizing enzyme and transporter microarray platform, in a retrospective case‐control study, the correlation between ADME polymorphic variants and grades ≥ 2−3‐Tr PN was investigated. In a breast cancer ( BC ) training set, five single‐nucleotide polymorphisms in NR 1I3 and UDP‐glucuronosyltransferase ( UGT ) 2B7 genes were correlated to grades ≥ 2−3‐Tr PN protection. By receiver operating characteristic curves, the grades ≥ 2−3‐Tr PN ‐related candidate biomarkers in an independent series of 54 patients with BC (17 cases and 37 controls) were validated. NR 1I3 was correlated to paclitaxel‐Tr PN and UGT 2B7 to docetaxel‐Tr PN . Moreover, a genetic signature of prognostic relevance for BC outcome was found. Our findings might have potential relevance for personalized management of patients with BC for prevention of treatment failure in ultrametabolizer genetic variants.