CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence

Melo,Mariella De Ameida; De Vasconcelos‑Valença,Rodrigo José; Neto,Fidelis Manes; Borges,Rafael Soares; Costa‑Silva,Danylo Rafhael; Barros‑Oliveira,Maria Da Conceição; Borges,Umbelina Soares; Alencar,Airlane Pereira; Silva,Vladimir Costa; Da Silva,Benedito Borges

doi:10.3892/br.2016.771

CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence

Authors:
- Mariella De Ameida Melo
- Rodrigo José De Vasconcelos‑Valença
- Fidelis Manes Neto
- Rafael Soares Borges
- Danylo Rafhael Costa‑Silva
- Maria Da Conceição Barros‑Oliveira
- Umbelina Soares Borges
- Airlane Pereira Alencar
- Vladimir Costa Silva
- Benedito Borges Da Silva
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Affiliations: Department of Gynecology, Federal University of Piauí, Health Sciences Center, Teresina, PI 64001‑020, Brazil, Department of Oncology, São Marcos Hospital, Teresina, PI 64001‑280, Brazil, Department of Mastology, Getulio Vargas Hospital, Federal University of Piauí, Teresina, PI 64001‑020, Brazil, Department of Statistics, State University of São Paulo, São Paulo, SP 05508‑900, Brazil, Department of Molecular Biology, Natan Portella Hospital, Federal University of Piaui, Teresina, PI 64001‑450, Brazil
Published online on: October 4, 2016 https://doi.org/10.3892/br.2016.771
Pages: 574-578

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Abstract

At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Thus, the aim of the present study was to investigate the association of the CYP2D6 *4, *10 and *17 gene polymorphisms with breast cancer recurrence in a Brazilian population. The cohort comprised 40 receptor‑positive breast cancer patients without recurrence and 40 with distant recurrence. A 3‑ml sample of peripheral blood was collected from each patient to determine the presence of the *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by quantitative polymerase chain reaction analysis. There was no statistically significant difference between the two groups regarding the polymorphism frequency (P=0.246). The results revealed that intermediate metabolizers occurred in 5% of patients without recurrence and in 15% of those with distant recurrence. Poor metabolizers occurred in only 1 patient (2.5%) per group, and there was no significant difference between the groups (P=0.789). The present study concluded that the CYP2D6 gene polymorphism in women with hormone‑sensitive breast cancer treated with tamoxifen was not associated with disease recurrence.

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1	Smith RA, Cokkinides V, Brooks D, Saslow D and Brawley OW: Cancer screening in the United States, 2010: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin. 60:99–119. 2010. View Article : Google Scholar : PubMed/NCBI
2	International Agency for Cancer Research, . Estimated Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/old/FactSheets/cancers/breast-new.aspAccessed. February 16–2016
3	Parkin DM and Fernández LM: Use of statistics to assess the global burden of breast cancer. Breast J. 12(Suppl 1): S70–S80. 2006. View Article : Google Scholar : PubMed/NCBI
4	Jankowitz RC, McGuire KP and Davidson NE: Optimal systemic therapy for premenopausal women with hormone receptor-positive breast cancer. Breast. 22(Suppl 2): S165–S170. 2013. View Article : Google Scholar : PubMed/NCBI
5	Montemurro F, Del Mastro L, De Laurentiis M and Puglisi F: Endocrine therapy in premenopausal women with breast cancer: A critical appraisal of current evidence. Expert Rev Anticancer Ther. 16:211–218. 2016. View Article : Google Scholar : PubMed/NCBI
6	Howlader N, Chen VW, Ries LA, Loch MM, Lee R, DeSantis C, Lin CC, Ruhl J and Cronin KA: Overview of breast cancer collaborative stage data items - their definitions, quality, usage, and clinical implications: A review of SEER data for 2004–2010. Cancer. 120(Suppl 23): 3771–3780. 2014. View Article : Google Scholar : PubMed/NCBI
7	Hoskins JM, Carey LA and McLeod HL: CYP2D6 and tamoxifen: DNA matters in breast cancer. Nat Rev Cancer. 9:576–586. 2009. View Article : Google Scholar : PubMed/NCBI
8	Motamedi S, Majidzadeh K, Mazaheri M, Anbiaie R, Mortazavizadeh SM and Esmaeili R: Tamoxifen resistance and CYP2D6 copy numbers in breast cancer patients. Asian Pac J Cancer Prev. 13:6101–6104. 2012. View Article : Google Scholar : PubMed/NCBI
9	Kiyotani K, Mushiroda T, Sasa M, Bando Y, Sumitomo I, Hosono N, Kubo M, Nakamura Y and Zembutsu H: Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy. Cancer Sci. 99:995–999. 2008. View Article : Google Scholar : PubMed/NCBI
10	Morrow PK, Serna R, Broglio K, Pusztai L, Nikoloff DM, Hillman GR, Fontecha M, Li R, Michaud L, Hortobagyi G, et al: Effect of CYP2D6 polymorphisms on breast cancer recurrence. Cancer. 118:1221–1227. 2012. View Article : Google Scholar : PubMed/NCBI
11	Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, et al: The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat. 101:113–121. 2007. View Article : Google Scholar : PubMed/NCBI
12	van Schaik RH: Cancer treatment and pharmacogenetics of cytochrome P450 enzymes. Invest New Drugs. 23:513–522. 2005. View Article : Google Scholar : PubMed/NCBI
13	Martins DM, Vidal FC, Souza RD, Brusaca SA and Brito LM: Determination of CYP2D6 3, 4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival. Braz J Med Biol Res. 47:1008–1015. 2014. View Article : Google Scholar : PubMed/NCBI
14	Schroth W, Antoniadou L, Fritz P, Schwab M, Muerdter T, Zanger UM, Simon W, Eichelbaum M and Brauch H: Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol. 25:5187–5193. 2007. View Article : Google Scholar : PubMed/NCBI
15	Karle J, Bolbrinker J, Vogl S, Kreutz R, Denkert C, Eucker J, Wischnewsky M, Possinger K and Regierer AC: Influence of CYP2D6-genotype on tamoxifen efficacy in advanced breast cancer. Breast Cancer Res Treat. 139:553–560. 2013. View Article : Google Scholar : PubMed/NCBI
16	De la Vega FM, Lazaruk KD, Rhodes MD and Wenz MH: Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System. Mutat Res. 573:111–135. 2005. View Article : Google Scholar : PubMed/NCBI
17	Abraham JE, Maranian MJ, Driver KE, Platte R, Kalmyrzaev B, Baynes C, Luccarini C, Shah M, Ingle S, Greenberg D, et al: CYP2D6 gene variants: Association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen. Breast Cancer Res. 12:R642010. View Article : Google Scholar : PubMed/NCBI
18	Ingelman-Sundberg M: Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 5:6–13. 2005. View Article : Google Scholar : PubMed/NCBI
19	Fukuda T, Yamamoto I, Nishida Y, Zhou Q, Ohno M, Takada K and Azuma J: Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers. Br J Clin Pharmacol. 47:450–453. 1999. View Article : Google Scholar : PubMed/NCBI
20	Goetz MP, Kamal A and Ames MM: Tamoxifen pharmacogenomics: The role of CYP2D6 as a predictor of drug response. Clin Pharmacol Ther. 83:160–166. 2008. View Article : Google Scholar : PubMed/NCBI
21	Toyama T, Yamashita H, Sugiura H, Kondo N, Iwase H and Fujii Y: No association between CYP2D6*10 genotype and survival of node-negative Japanese breast cancer patients receiving adjuvant tamoxifen treatment. Jpn J Clin Oncol. 39:651–656. 2009. View Article : Google Scholar : PubMed/NCBI
22	Irvin WJ Jr, Walko CM, Weck KE, Ibrahim JG, Chiu WK, Dees EC, Moore SG, Olajide OA, Graham ML, Canale ST, et al: Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: A multicenter study. J Clin Oncol. 29:3232–3239. 2011. View Article : Google Scholar : PubMed/NCBI