The risk of recurrence in breast cancer patients treated with tamoxifen: Polymorphisms of CYP2D6 and ABCB1

L. K. Teh, N. I. Mohamed, M. Z. Salleh, Rohaizak Muhammad, Shahrun Niza Abdullah Suhaimi, Saladina Jaszle Jasmin, J. K S Shia, H. Roslan, S. Sood, T. S. Rajoo, S. P. Muniandy, G. Henry, H. A. Ngow, K. T. Hla U, J. Din

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Abstract

CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P=0.004) than patients with CYP2D6*1/*1 and*1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P=0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI=0.79-23.2) compared to those without this combination which was 48 months (95% CI=14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalAAPS Journal
Volume14
Issue number1
DOIs
Publication statusPublished - Mar 2012

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Cytochrome P-450 CYP2D6
Tamoxifen
Breast Neoplasms
Recurrence
Genotype
Alleles
Kaplan-Meier Estimate
P-Glycoprotein
Neoplasm Metastasis
Drug Therapy
Polymerase Chain Reaction

Keywords

  • ABCB1
  • breast cancer
  • CYP2D6
  • recurrence and metastasis
  • tamoxifen

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

The risk of recurrence in breast cancer patients treated with tamoxifen : Polymorphisms of CYP2D6 and ABCB1. / Teh, L. K.; Mohamed, N. I.; Salleh, M. Z.; Muhammad, Rohaizak; Abdullah Suhaimi, Shahrun Niza; Jasmin, Saladina Jaszle; Shia, J. K S; Roslan, H.; Sood, S.; Rajoo, T. S.; Muniandy, S. P.; Henry, G.; Ngow, H. A.; Hla U, K. T.; Din, J.

In: AAPS Journal, Vol. 14, No. 1, 03.2012, p. 52-59.

Research output: Contribution to journalArticle

Teh, LK, Mohamed, NI, Salleh, MZ, Muhammad, R, Abdullah Suhaimi, SN, Jasmin, SJ, Shia, JKS, Roslan, H, Sood, S, Rajoo, TS, Muniandy, SP, Henry, G, Ngow, HA, Hla U, KT & Din, J 2012, 'The risk of recurrence in breast cancer patients treated with tamoxifen: Polymorphisms of CYP2D6 and ABCB1', AAPS Journal, vol. 14, no. 1, pp. 52-59. https://doi.org/10.1208/s12248-011-9313-6
Teh, L. K. ; Mohamed, N. I. ; Salleh, M. Z. ; Muhammad, Rohaizak ; Abdullah Suhaimi, Shahrun Niza ; Jasmin, Saladina Jaszle ; Shia, J. K S ; Roslan, H. ; Sood, S. ; Rajoo, T. S. ; Muniandy, S. P. ; Henry, G. ; Ngow, H. A. ; Hla U, K. T. ; Din, J. / The risk of recurrence in breast cancer patients treated with tamoxifen : Polymorphisms of CYP2D6 and ABCB1. In: AAPS Journal. 2012 ; Vol. 14, No. 1. pp. 52-59.
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