Revisiting Breast Cancer Outcomes in Concomitant Users of Tamoxifen and Selective Serotonin Reuptake Inhibitors

In a recent Canadian study that involved breast cancer survivors who used tamoxifen, concomitant use of the selective serotonin reuptake inhibitor (SSRI) paroxetine was associated with excess breast cancer mortality. Researchers speculated that this finding was caused by paroxetine's inhibition of cytochrome P450 (CYP) 2D6 (a hepatic enzyme that converts tamoxifen to its active metabolite; JW Womens Health Mar 4 2010). But could poor tamoxifen adherence play a role? In a study designed to evaluate the association of concomitant tamoxifen and CYP2D6 inhibitor use on adherence and breast cancer outcomes, Dutch investigators linked national cancer registry and pharmacy data for women with breast cancer who received both tamoxifen and one of several possible CYP2D6 inhibitors (including the potent inhibitors paroxetine and fluoxetine). Tamoxifen adherence was calculated based on the percentage of days of use in the first year following prescription initiation.

Of 1962 eligible patients (mean age at diagnosis, 60) for whom tamoxifen was prescribed, 150 also had been prescribed a CYP2D6 inhibitor for >60 days (82 used paroxetine, and 25 used fluoxetine). Overall mean adherence to tamoxifen was 93% at 1 year; among users of paroxetine or fluoxetine, adherence was 90% (P=0.007). Breast cancer event–free time (EFT) was similar between CYP2D6-inhibitor users and nonusers. In contrast, poor tamoxifen adherence was significantly associated with unfavorable EFT: women with ≥90% tamoxifen adherence had 27% lower risk for breast cancer events than did women with <90% adherence.