CYP2D6 Inhibitors Not Linked to Breast Cancer Recurrence

Study finds no association in early-stage breast cancer patients on adjuvant tamoxifen

FRIDAY, April 16 (HealthDay News) -- Despite a strong biologic rationale, there may be no association between concomitant usage of cytochrome P450 2D6 (CYP2D6) inhibitors such as selective serotonin reuptake inhibitors and breast cancer recurrence in patients with early-stage disease who are treated with adjuvant tamoxifen, though there is an association between poor tamoxifen adherence and increased risk of breast cancer events, according to a study published online April 12 in the Journal of Clinical Oncology.

Vincent O. Dezentjé, M.D., of the Leiden University Medical Center in the Netherlands, and colleagues analyzed data on 1,962 patients who were treated with adjuvant tamoxifen between 1994 and 2006, including 150 (7.6 percent) who frequently used a CYP2D6 inhibitor during treatment.

The researchers observed no association between concomitant usage of CYP2D6 inhibitors and breast cancer recurrence (adjusted hazard ratio [aHR], 0.87; P = .69). However, they found that poor tamoxifen adherence was associated with lower breast cancer event-free time (aHR, 0.987; P = .029). Compared to patients with 80 percent or less or 90 percent or less adherence, they found that those with at least 80 percent or at least 90 percent adherence had a reduced risk of a breast cancer event (26 and 27 percent, respectively).

"On the basis of these study results and present literature, there is insufficient evidence to withhold CYP2D6 inhibitors from patients during tamoxifen therapy," the authors write. "However, at the 45th Annual Meeting of the American Society of Clinical Oncology in 2009, a study similar to ours was presented showing an almost two-fold increased breast cancer recurrence risk in CYP2D6 inhibitor users compared with tamoxifen only users. Given these results and the strong mechanistic model, caution is warranted. We suggest using non-CYP2D6 inhibitors whenever possible while additional studies are awaited."

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