Abstract
Tamoxifen reduces recurrence risk among women treated for estrogen receptor-positive breast cancer. Its effectiveness partly depends on metabolic activation via cytochrome P450 2D6 (CYP2D6). Some medications compromise CYP2D6 activity and may lower plasma concentrations of active tamoxifen metabolites. We studied the association between concurrent use of tamoxifen and CYP2D6-inhibiting medications and breast cancer recurrence among Danish women diagnosed with early-stage, estrogen receptor-positive breast cancer. Using the Danish Breast Cancer Cooperative Group Registry, we identified 366 cases with local or distant breast cancer recurrence and 366 matched breast cancer controls. We ascertained concurrent prescription of CYP2D6-inhibiting medications during tamoxifen treatment by linking to the national prescription database covering all Danish pharmacies. We computed the breast cancer recurrence odds ratio (OR) and 95% confidence interval for each medication. The pooled recurrence OR was null (OR, 1.0; 95% confidence interval, 0.8-1.3); recurrence ORs for individual drugs ranged from 0.3 to 3.4. The individual ORs followed the pattern expected under a null-centered Gaussian distribution. Null associations were apparent for all drugs after empirical Bayes adjustment for multiple comparisons. Together, these results provide evidence for a null association between drug-compromised CYP2D6 activity and breast cancer recurrence among tamoxifen-treated women.