Concurrent use of tamoxifen with CYP2D6 inhibitors and the risk of breast cancer recurrence

Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. However, it is still unclear whether such concurrent use affects tamoxifen’s effectiveness. Thus, the objective of this study is to determine whether concurrent use of tamoxifen with CYP2D6 inhibitors increases the risk of recurrence in patients newly diagnosed with breast cancer. We conducted a nested case–control analysis within a population-based cohort from the UK General Practice Research Database. The cohort included women with a first-ever diagnosis of breast cancer who were prescribed tamoxifen between January 1, 1998 and June 30, 2008. Cases consisted of all patients with a breast cancer recurrence occurring during follow-up. Up to ten controls were matched to each case on year of birth, date of cohort entry, and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RR) of breast cancer recurrence in patients who concurrently used tamoxifen with CYP2D6 inhibitors, compared to patients who only used tamoxifen. The cohort included 9,209 incident users of tamoxifen, of whom 807 were diagnosed with a breast cancer recurrence. Concurrent use was not associated with an increased incidence of breast cancer recurrence (adjusted RR 1.07, 95% 0.88, 1.30). Type and strength of CYP2D6 inhibitors, as well as duration of concurrent use did not affect breast cancer recurrence. These results remained consistent after performing sensitivity analyses. The results of this large population-based study indicate that concurrent use of tamoxifen with CYP2D6 inhibitors does not increase the risk of recurrence.