38P - Breast Cancer Pharmacogenetics: Case Control study on TAM adjuvant treatment outcome.

Date 04 May 2017
Event IMPAKT 2017
Session Welcome reception and Poster Walk
Topics Breast Cancer
Presenter Sunishtha Yadav
Authors S.S. Yadav, V. Chauhan
  • Biosciences, Amity Institute of Biotechnology, 201303 - Noida/IN

Abstract

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INTRODUCTION: Cytochrome P4502D6 (CYP2D6) is of great pharmacogenetics interest due to its involvement in the biotransformation of Tamoxifen to the active metabolite endoxifen. And therefore, variations in the activity of CYP2D6 enzyme due to genetic polymorphisms may alter activity directly affecting the concentrations of active tamoxifen metabolites. CYP2D6*4 (G1934A), located on intron 3 and exon 4 junction, and CYP2D6*10 allele (C100T at exon 1), results in decreased catalytic activity of the enzyme and may lead to inappropriate metabolism of this drug thus, leading to variation in treatment outcome. Therefore, pharmacogenetics studies will help in standardization of chemotherapeutic drugs and better treatment outcome in breast cancer patients (precision medicine) carrying variant genotypes of CYP2D6.

OBJECTIVE: The present study was undertaken to investigate the association of variant genotypes of CYP2D6 with the treatment response (personalized medicine approach) in Breast cancer cases receiving adjuvant tamoxifen.

METHODOLOGY: 300 patients suffering from Breast cancer and equal number of age matched controls were included in the study. Genomic DNA was isolated from the blood samples and CYP2D6 genotypes were determined in genomic DNA by PCR based RFLP. Follow-up carried out to correlate the association (if any) in between variants and treatment outcome. Chi-square test and logistic regression models were used to determinate association between genotype, use of concomitant CYP2D6 inhibitors and disease relapse rate.

RESULTS & DISCUSSION: The frequency of variant alleles of CYP2D6 (CYP2D6*4 & *10) was found to be significantly higher in the cases when compared to the controls. The variant genotypes have lower benefit of TAM adjuvant treatment and tend to have a higher risk of disease relapse. This study further suggest that the presence of the inactive CYP2D6*4 & *10 causes a reduction in the metabolic activation of anticancer agents, thereby lowering the risk of toxicity but worsening the therapeutic response. Further research into CYP2D6 may provide more insights that will aid in the development of immunotherapy for breast cancer.

KEYWORDS: Adjuvant chemotherapy, CYP2D6, pharmacogenetics, tamoxifen

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