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

Jacqueline M. Dempsey, Kelley M. Kidwell, Christina L. Gersch, Andrea M. Pesch, Zeruesenay Desta, Anna Maria Storniolo, Vered Stearns, Todd C. Skaar, Daniel F. Hayes, N. Lynn Henry, James M. Rae, Daniel L. Hertz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalPharmacogenomics
Volume20
Issue number8
DOIs
StatePublished - Jan 1 2019

Keywords

  • SLCO1B1
  • breast cancer
  • exemestane
  • letrozole
  • pharmacogenomics

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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