Work

Germline Genetic Predictors of Aromatase Inhibitor Concentrations, Estrogen Suppression and Drug Efficacy and Toxicity in Breast Cancer Patients

Year: 2017

Type: article

Abstract: The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants. This review summarizes published germline genetic associations with AI treatment outcomes including systemic AI concentrations, estrogenic response to AIs, AI treatment efficacy and AI treatment toxicities. Significant associations are highlighted with commentary about prioritization for future validation to identify pharmacogenetic predictors of AI treatment outcomes that can be used to inform personalized treatment decisions in patients with estrogen receptor-positive breast cancer.

Source: Pharmacogenomics

DOI: 10.2217/pgs-2016-0205

Authors: Daniel L Hertz, N Lynn Henry, James M Rae

Institutions: University of Michigan, University of Utah, Huntsman Cancer Institute, U-M Rogel Cancer Center

Language: English

Topic: Pharmacogenetics and Drug Metabolism

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Breast Cancer Research Foundation, National Institute of General Medical Sciences