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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2018

01-11-2018 | Clinical trial

Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer

Authors: Adrienne E. Borrie, Rhiannon V. Rose, Yun-Hee Choi, Francisco E. Perera, Nancy Read, Tracy Sexton, Michael Lock, Theodore A. Vandenberg, Karin Hahn, Robert Dinniwell, Jawaid Younus, Diane Logan, Kylea Potvin, Brian Yaremko, Edward Yu, John Lenehan, Stephen Welch, Rachel F. Tyndale, Wendy A. Teft, Richard B. Kim

Published in: Breast Cancer Research and Treatment | Issue 2/2018

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Abstract

Purpose

The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia.

Methods

We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms.

Results

More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and positively associated with plasma letrozole concentrations, respectively. CYP2A6 genotype was significantly associated with letrozole levels (P < 0.0001), and increased plasma letrozole levels were observed in patients with CYP2A6 reduced-function genotypes. Plasma levels of letrozole and CYP2A6 genotype were not significantly associated with a change in pain score from baseline.

Conclusions

CYP2A6 genotype was a significant predictor of letrozole plasma levels, but was not associated with the development of arthralgia.
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Metadata
Title
Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer
Authors
Adrienne E. Borrie
Rhiannon V. Rose
Yun-Hee Choi
Francisco E. Perera
Nancy Read
Tracy Sexton
Michael Lock
Theodore A. Vandenberg
Karin Hahn
Robert Dinniwell
Jawaid Younus
Diane Logan
Kylea Potvin
Brian Yaremko
Edward Yu
John Lenehan
Stephen Welch
Rachel F. Tyndale
Wendy A. Teft
Richard B. Kim
Publication date
01-11-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4910-z

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