Abstract

Tamoxifen is a non-steroidal antiestrogen drug widely used in the treatment of breast cancer and metabolized by CYP2D6.  In this study, we compared the patients who were receiving either tamoxifen or other chemo drugs, forming a two-arm study.  We genotyped 140 tamoxifen treated postmenopausal women with breast cancer, 140 non-tamoxifen treated pre and postmenopausal women with breast cancer and 124 controls, using  PCR-RFLP method. In arm-1 study CYP2D6 genotype frequencies of metabolizers were classified as extensive metabolizers (EM) 70% (n = 98), intermediate metabolizers (IM) 30% (n = 42) in tamoxifen treated cases and 85% (n = 118), 15% (n = 22) in non-tamoxifen treated cases respectively. Tamoxifen treated IM -carriers showed 24.32% (n = 9) recurrence. Recurrent cases were not found in non-tamoxifen treated group.  CYP2D6*4 allele carriers were high but this allele carrier was found to reduce the risk of recurrence when treated with tamoxifen. In arm-2 study CYP2D6 genotype frequencies of EM, IM and Poor metabolizers (PM) were 79.57% (n = 113), 14.08% (n = 20), 6.33% (n = 9) in non tamoxifen treated breast cancer cases. In controls the EM, IM, and PM genotypes were 93.54% (n = 116), 5.64%) (n = 7) and 0.80% (n = 1) respectively. Statistical analysis indicated that p value of both IM (P- value 0.03) and PM (P- value 0.04) carriers were associated with the risk of breast cancer. PM showed poor therapeutic outcome, which may be due to low level of the tamoxifen metabolite-endoxifen.

Key words: Breast cancer, Tamoxifen, CYP2D6*4, Poor metabolizers (PM), Extensive metabolizers (EM), Intermediate metabolizers (IM).

Tamoxifen is a non-steroidal antiestrogen drug widely used in the treatment of breast cancer and metabolized by CYP2D6.  In this study, we compared the patients who were receiving either tamoxifen or other chemo drugs, forming a two-arm study.  We genotyped 140 tamoxifen treated postmenopausal women with breast cancer, 140 non-tamoxifen treated pre and postmenopausal women with breast cancer and 124 controls, using  PCR-RFLP method. In arm-1 study CYP2D6 genotype frequencies of metabolizers were classified as extensive metabolizers (EM) 70% (n = 98), intermediate metabolizers (IM) 30% (n = 42) in tamoxifen treated cases and 85% (n = 118), 15% (n = 22) in non-tamoxifen treated cases respectively. Tamoxifen treated IM -carriers showed 24.32% (n = 9) recurrence. Recurrent cases were not found in non-tamoxifen treated group.  CYP2D6*4 allele carriers were high but this allele carrier was found to reduce the risk of recurrence when treated with tamoxifen. In arm-2 study CYP2D6 genotype frequencies of EM, IM and Poor metabolizers (PM) were 79.57% (n = 113), 14.08% (n = 20), 6.33% (n = 9) in non tamoxifen treated breast cancer cases. In controls the EM, IM, and PM genotypes were 93.54% (n = 116), 5.64%) (n = 7) and 0.80% (n = 1) respectively. Statistical analysis indicated that p value of both IM (P- value 0.03) and PM (P- value 0.04) carriers were associated with the risk of breast cancer. PM showed poor therapeutic outcome, which may be due to low level of the tamoxifen metabolite-endoxifen.

Key words: Breast cancer, Tamoxifen, CYP2D6*4, Poor metabolizers (PM), Extensive metabolizers (EM), Intermediate metabolizers (IM).