Association of CYP2D6 metabolizer status with mammographic density change in response to tamoxifen treatment

INTRODUCTION: Not all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition. As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate the association between germline CYP2D6 polymorphisms and PMD change. METHODS: Baseline and follow-up mammograms were retrieved for 278 tamoxifen-treated subjects with CYP2D6 metabolizer status (extensive (EM), heterozygous extensive/intermediate (hetEM/IM) or poor metabolizer (PM)). Logistic regression analyses were conducted comparing subjects who experienced >10% reduction in PMD to those who experienced ≤10% reduction or increase. RESULTS: After multivariate adjustment, PMD change was found to be significantly associated with the degree of CYP2D6 enzyme functionality (Ptrend = 0.021). Compared with EM, hetEM/IM and PM were 72% (95% confidence interval (CI): 0.10 to 0.79) and 71% (0.03 to 2.62) less likely to experience a >10% reduction, respectively. CONCLUSIONS: Tamoxifen-induced change in PMD appears to have a genetic component.