Paroxetine Use Negates Benefits of Tamoxifen in Women with Breast Cancer

Tamoxifen is a prodrug; conversion to its active metabolite, endoxifen, is catalyzed by cytochrome P₄₅₀ isoenzyme 2D6 (CYP2D6). In women with estrogen-receptor–positive early-stage breast cancer, use of tamoxifen lowers risk for recurrent breast cancer by one half and risk for death due to breast cancer by one third. Many such women also are treated with selective serotonin reuptake inhibitors (SSRIs) for depression and tamoxifen-associated hot flashes. SSRIs, particularly paroxetine, inhibit CYP2D6, thus raising concerns that SSRI use might negate benefits conferred by tamoxifen. In this population-based cohort study, investigators determined whether SSRI use was associated with excess mortality in women with breast cancer who received tam…