Risk of Breast Cancer Recurrence in Women Initiating Tamoxifen with CYP2D6 Inhibitors

Authors: Ronald E. Aubert, PhD,¹ Eric J. Stanek, PharmD,¹ Jianying Yao, MS,¹ J. Russell Teagarden, MA, DMH,¹ Milayna Subar, MD,¹ Robert S. Epstein, MD,¹ Todd C. Skaar, PhD,² Zeruesenay Desta, PhD,² David A. Flockhart, MD, PhD.²

Presented May 30, 2009, at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting.

Study in Brief:
- Tamoxifen is metabolized to its active form, endoxifen, by hepatic cytochrome P450 (CYP) 2D6. Concurrent use of pharmacologic inhibitors of CYP2D6 with tamoxifen can significantly reduce endoxifen plasma concentrations.

- This analysis examines the clinical impact of CYP2D6 inhibitor medications on the rate of breast cancer recurrence in women being treated with tamoxifen.

- The study was a retrospective analysis of almost 1,300 women who had been newly prescribed tamoxifen to treat breast cancer between 2003 and 2005 and were followed for at least two years. All patients included in the study were required to be at least 70 percent compliant with their tamoxifen therapy; patients on average, were 90 percent compliant throughout the study period.

- Two groups of patients were identified. One cohort included 353 patients who, in addition to their tamoxifen treatment, were also taking any medication known to be a potent or moderate CYP2D6 inhibitor; the average duration of concurrent use of both drugs was 340 days. The second cohort was made up of 945 patients on tamoxifen therapy who were not using a CYP2D6 inhibitor during the study period.

- Results showed patients taking a potent or moderate CYP2D6 inhibitor while using tamoxifen had a statistically significant 1.9-fold higher two-year breast cancer recurrence rate of 13.9 percent as compared with 7.5 percent for patients using only tamoxifen.

- A subsequent analysis focused on 60 percent of the women on a CYP2D6 inhibitor who were taking selective serotonin reuptake inhibitors (SSRIs). This SSRI subset included 213 women on potent or moderate CYP2D6 inhibitor SSRIs [Prozac^® (fluoxetine), Paxil^® (paroxetine) and Zoloft^® (sertraline)], and 137 women using weak CYP2D6 inhibitor SSRIs [Celexa® (citalopram), Lexapro^® (escitalopram), and Luvox^® (fluvoxamine)].

- Women on a moderate or potent CYP2D6 inhibitor SSRI had a breast cancer recurrence rate of 16 percent, while patients using a weak CYP2D6 inhibitor SSRI showed a breast cancer recurrence not significantly different from that in women receiving tamoxifen alone.

¹Medco Health Solutions, Inc., Franklin Lakes, NJ
²Indiana University School of Medicine, Indianapolis, IN.