32P - Pharmacogenomics of aromatase inhibitor associated arthralgia in patients with ER+ breast cancer

Date 04 May 2017
Event IMPAKT 2017
Session Welcome reception and Poster Walk
Topics Biomarkers
Breast Cancer
Translational Research
Presenter Adrienne Borrie
Authors A.E. Borrie1, W.A. Teft1, R.B. Kim2
  • 1Clinical Pharmacology, University of Western Ontario, N6A 5A5 - London, Ontario/CA
  • 2Medicine, University of Western Ontario, N6A 5A5 - London, Ontario/CA

Abstract

Body

Aromatase inhibitors (AIs) are the most commonly used first-line endocrine treatment for postmenopausal women with estrogen receptor-positive (ER+) breast cancer (BC), but AI activity varies widely among patients. Significant adverse drug reactions (ADRs) are associated with AIs, the most common being arthralgia. We hypothesize that a more comprehensive assessment of pharmacogenetic and pharmacokinetic variables that affect AI disposition will improve AI selection and dosing for BC patients. BC patients initiating AI therapy (n = 135) were recruited at the London Regional Cancer Program. Patients completed questionnaires regarding arthralgia symptoms and provided blood samples at baseline, 6 weeks and 6 months after AI initiation. Plasma AI drug concentration was measured by liquid chromatography tandem mass-spectrometry (LC-MS/MS). DNA was extracted and used for pharmacogenetic analysis of CYP3A4 and CYP2A6. To date, 135 patients have completed their baseline visit. Of these, 95 patients have completed follow-up questionnaires and blood work at 6 weeks. More than half (55%) of patients have had measurable increases in pain in their hands, shoulders, and arms, and 45% of patients have had measurable increases in pain in their hips and knees. A preliminary LC-MS/MS analysis from 55 patients on letrozole has shown that plasma concentrations of letrozole are significantly (p = 0.0061) associated with CYP2A6 variation. Understanding the impact of genes and drug levels on AI-induced ADRs will help clinicians better manage AI therapy and facilitate personalized medicine for women with BC.

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