CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset.

The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence. CYP2C19 genotype data was available for 2 423 patients and the final sample cohort comprised 2 102 patients. CYP2C192 or 19 alleles did not influence DFS. For the CYP2C192 allele, the HR was 1.05 (CI 0.78-1.42) and 0.79 (CI 0.32-1.94) for hetero- and homozygote carriers, respectively. The corresponding HR for hetero- and homozygote carriers of the CYP2C1917 allele were 1.02 (CI 0.71-1.46) and 0.57 (CI 0.26-1.24), respectively. Accounting for CYP2D6 genotype status did not change these estimates. We found no evidence to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breast cancer patients and, consequently, CYP2C19 genotype status should not be included in clinical decisions on tamoxifen treatment.