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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.

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


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.


; breast cancer; exemestane; letrozole; pharmacogenomics


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