Effects of SLCO1B1 Polymorphisms on Plasma Estrogen Concentrations in Women with Breast Cancer Receiving Aromatase Inhibitors Exemestane and Letrozole

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
• SLCO1B1

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.futuremedicine.com/doi/suppl/10.2217/pgs-2019-0020

Acknowledgments

The authors wish to posthumously recognize D Flockhart, who co-chaired the COnsortium on BReast cancer phArmacogomics (COBRA) and passed during preparation of this manuscript.

Financial & competing interests disclosure

This research was supported by Pharmacogenetics Research Network Grant Number U-01 GM61373 David A Flockhart (DAF) and Clinical Pharmacology Training Grant Number 5T32-GM08425 (DAF) from the National Institute of General Medical Sciences, NIH from Grant Numbers M01-RR000042 (University of Michigan), M01-RR00750 (Indiana University) and M01-RR00052 (Johns Hopkins University) from the National Center for Research Resources (NCRR), a component of the NIH, the Breast Cancer Research Foundation (BCRF; N003173 to JM Rae and DF Hayes), the National Cancer Institute (5T32CA083654-12, PI Jeremy Taylor), the National Institute of General Medical Sciences (GM099143 to JM Rae) and the NIH through the University of Michigan’s Cancer Center Support Grant (P30 CA046592) by the use of the following Cancer Center Core: University of Michigan DNA Sequencing Core. In addition, these studies were supported by grants from Pfizer (DF Hayes), Novartis Pharma AG (DF Hayes), the Fashion Footwear Association of New York/QVC Presents Shoes on Sale (DF Hayes). Drugs were supplied by Novartis and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This research was supported by Pharmacogenetics Research Network Grant Number U-01 GM61373 David A Flockhart (DAF) and Clinical Pharmacology Training Grant Number 5T32-GM08425 (DAF) from the National Institute of General Medical Sciences, NIH from Grant Numbers M01-RR000042 (University of Michigan), M01-RR00750 (Indiana University) and M01-RR00052 (Johns Hopkins University) from the National Center for Research Resources (NCRR), a component of the NIH, the Breast Cancer Research Foundation (BCRF; N003173 to JM Rae and DF Hayes), the National Cancer Institute (5T32CA083654-12, PI Jeremy Taylor), the National Institute of General Medical Sciences (GM099143 to JM Rae) and the NIH through the University of Michigan’s Cancer Center Support Grant (P30 CA046592) by the use of the following Cancer Center Core: University of Michigan DNA Sequencing Core. In addition, these studies were supported by grants from Pfizer (DF Hayes), Novartis Pharma AG (DF Hayes), the Fashion Footwear Association of New York/QVC Presents Shoes on Sale (DF Hayes). Drugs were supplied by Novartis and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.