In a premenopausal woman with low risk, early stage HR-positive breast cancer who is unable to discontinue a strong CYP2D6 inhibitor, do you use still utilize tamoxifen versus an AI with ovarian suppression?

CYP2D6 enzymes metabolize tamoxifen to the active metabolite endoxifene. There are variants alleles of the the 2D6 enzyme such that depending on the inheritance of one or two variant alleles one makes less endoxifene. Testing for variant alleles is clinically available, however, the results of studies that relate variant alleles to the clinical outcomes of tamoxifen efficacy are conflicting. Therefore, no testing is necessary or recommended prior to starting tamoxifen.

This case described deals...

In my practice, I try to avoid the strong CYP2D6 inhibitors when I plan to prescribe tamoxifen (e.g. for low risk hormone-receptor positive breast cancer in a young premenopausal woman). Tamoxifen relies on the CYP2D6 enzyme to be converted to its active metabolite, endoxifen. I discuss the use of other less potent inhibitors of CYP2D6, ideally venlafaxine (although I think citalopram and escitalopram are probably acceptable as well). (Ref: https://www.ncbi.nlm.nih.gov/pubmed/27694573)