CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients.

BACKGROUND

CYP2C8/9 polymorphisms may influence breast cancer-free survival after diagnosis due to their role in the metabolism of tamoxifen, paclitaxel, and other chemotherapy. cytochrome P450 (CYP)2C8/9 metabolise arachidonic acid to epoxyeicosatrienoic acids, which enhance migration and invasion in vitro and promote angiogenesis in vivo. We aimed to investigate the frequency of CYP2C8/9 polymorphisms in relation to breast tumour characteristics and disease-free survival.

METHODS

A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C83, CYP2C84, CYP2C92, and CYP2C93. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports.

RESULTS

Frequencies of CYP2C8/9 polymorphisms were similar to healthy European populations. Significantly less node involvement (P=0.002) and fewer PR+ tumours (P=0.012) were associated with CYP2C84. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/93/1/*2/1 was the only factor associated with increased risk for early events in 297 tamoxifen-treated, ER-positive patients, adjusted HR 2.54 (95%CI 1.11-5.79). The effect appeared to be driven by CYP2C83, adjusted HR 8.56 (95%CI 1.53-51.1).

CONCLUSION

Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients.