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 CYP2C8* 3, CYP2C8* 4, CYP2C9* 2, and CYP2C9* 3. 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 CYP2C8* 4. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/9* 3/* 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 CYP2C8* 3, 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.