Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.

PURPOSE

The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B64 (rs2279343), CYP2B65 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy.

METHODS

A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients.

RESULTS

The minor allele frequencies of CYP2B69, CYP2B64 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity.

CONCLUSIONS

This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.