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Pharmacogenomics. 2019 Jun;20(8):571-580. doi: 10.2217/pgs-2019-0020.

Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole.

Author information

1
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109-1065, USA.
2
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
3
Department of Internal Medicine, Division of Hematology/Oncology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
4
Department of Medicine, Indiana University, Indianapolis, IN 46202, USA.
5
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.

Abstract

Aim: This study tested for associations between SLCO1B1 polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Patients & methods: Postmenopausal women with hormone-receptor positive breast cancer were genotyped for SLCO1B1*5 (rs4149056) and rs10841753. Pretreatment and on-treatment plasma estrogens and aromatase inhibitor (AI) concentrations were measured. Regression analyses were performed to test for pharmacogenetic associations with estrogens and drug concentrations. Results: SLCO1B1*5 was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3 months of AI treatment. Conclusion: These findings suggest SLCO1B1 polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.

KEYWORDS:

; breast cancer; exemestane; letrozole; pharmacogenomics

PMID:
31190621
DOI:
10.2217/pgs-2019-0020

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