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

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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 language	English (US)
Pages (from-to)	571-580
Number of pages	10
Journal	Pharmacogenomics
Volume	20
Issue number	8
DOIs	https://doi.org/10.2217/pgs-2019-0020
State	Published - 2019

Keywords

SLCO1B1
breast cancer
exemestane
letrozole
pharmacogenomics

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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10.2217/pgs-2019-0020

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Dempsey, J. M., Kidwell, K. M., Gersch, C. L., Pesch, A. M., Desta, Z., Storniolo, A. M., Stearns, V., Skaar, T. C., Hayes, D. F., Henry, N. L., Rae, J. M., & Hertz, D. L. (2019). Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole. Pharmacogenomics, 20(8), 571-580. https://doi.org/10.2217/pgs-2019-0020

Dempsey, JM, Kidwell, KM, Gersch, CL, Pesch, AM, Desta, Z, Storniolo, AM, Stearns, V, Skaar, TC, Hayes, DF, Henry, NL, Rae, JM & Hertz, DL 2019, 'Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole', Pharmacogenomics, vol. 20, no. 8, pp. 571-580. https://doi.org/10.2217/pgs-2019-0020

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title = "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 = "SLCO1B1, breast cancer, exemestane, letrozole, pharmacogenomics",

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

note = "Publisher Copyright: {\textcopyright} 2019 Future Medicine Ltd.",

year = "2019",

doi = "10.2217/pgs-2019-0020",

language = "English (US)",

volume = "20",

pages = "571--580",

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AU - Dempsey, Jacqueline M.

AU - Kidwell, Kelley M.

AU - Gersch, Christina L.

AU - Pesch, Andrea M.

AU - Desta, Zeruesenay

AU - Storniolo, Anna Maria

AU - Stearns, Vered

AU - Skaar, Todd C.

AU - Hayes, Daniel F.

AU - Henry, N. Lynn

AU - Rae, James M.

AU - Hertz, Daniel L.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - SLCO1B1

KW - breast cancer

KW - exemestane

KW - letrozole

KW - pharmacogenomics

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

Abstract

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