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Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

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Abstract

Ethnic differences in patient genetics and breast cancer (BC) biology contribute to ethnic disparities in cancer presentation and patient outcome. We prospectively evaluated SNPs within phase I and phase II tamoxifen (TAM) metabolizing enzymes, and the estrogen receptor gene (ESR1), aiming to identify potential pharmacogenomic ethnicity patterns in an ER-positive BC cohort constituted of Hispanic and Non-Hispanic White (NHW) women in South Texas. Plasma concentrations of TAM/metabolites were measured using HPLC. CYP2C9, CYP2D6 and SULT1A1 genotypes were determined by DNA sequencing/Pyrosequencing technology. ESR1 PvuII and XbaI SNPs were genotyped using Applied Biosystems Taqman® Allelic Discrimination Assay. Hispanics had higher levels of TAM, 4-hydroxytamoxifen, and endoxifen than NHWs. There was a higher prevalence of CYP2D6 EM within Hispanics than NHWs, which corresponded to higher endoxifen levels, but no differences were verified with regard to CYP2C9 and SULT1A1. We found a higher incidence of the wild type forms of the ESR1 in Hispanics than NHWs. The performance status, the disease stage at diagnosis, and the use of aromatase inhibitors might have overcome the overall favorable pharmacogenomics profile of Hispanics when compared to NHWs in relation to TAM therapy responsiveness. Our data strongly point to ethnical peculiarities related to pharmacogenomics and demographic features of TAM treated Hispanics and NHWs. In the era of pharmacogenomics and its ultimate goal of individualized, efficacious and safe therapy, cancer studies focused on the Hispanic population are warranted because this is the fastest growing major demographic group, and an understudied segment in the U.S.

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Acknowledgments

The present work was supported in part by the American Foundation for Pharmaceutical Education Post-Pharm.D. Fellowship, the Cancer Center Council Grant, and the San Antonio Cancer Institute NCI Cancer Center Support Grant P30 CA054174. LBAR was supported by The National Council for Scientific and Technological Development (CNPq)/Ciencias sem Fronteiras Program, Brazil.

Ethical standards

Experiments comply with current U.S. laws. All patients provided informed written consent prior to participation, and the study was conducted in accordance with the ethical standards of the University of Texas Health Sciences Center at San Antonio Institutional Review Board and the San Antonio Cancer Institute Protocol Review Committee.

Conflict of interest and disclosure

The authors declare that they have no conflicts of interest or financial disclosures.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Biotechnology Program/RENORBIO, Health Sciences Center, Universidade Federal do Espirito Santo, Av. Marechal Campos, 1468, Maruipe, Vitoria, ES, 29040-090, Brazil

    Leticia B. A. Rangel

  2. College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX, 78712, USA

    Leticia B. A. Rangel, Christopher R. Frei & John G. Kuhn

  3. School of Medicine, Pharmacotherapy Education and Research Center, The University of Texas Health Sciences Center at San Antonio, 8403 Floyd Curl Dr., San Antonio, TX, 78229, USA

    Leticia B. A. Rangel, Christopher R. Frei & John G. Kuhn

  4. Investigational Drug Section, Cancer Therapy and Research Center, The University of Texas Health Sciences Center at San Antonio, 7979 Wurzbach Rd, San Antonio, TX, 78229, USA

    Jodi L. Taraba

  5. The START Center for Cancer Care, 4383 Medical Dr, San Antonio, TX, 78229, USA

    Lon Smith & Gladys Rodriguez

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  1. Leticia B. A. Rangel
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Correspondence to John G. Kuhn.

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Rangel, L.B.A., Taraba, J.L., Frei, C.R. et al. Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer. Breast Cancer Res Treat 148, 571–580 (2014). https://doi.org/10.1007/s10549-014-3191-4

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