Predicting Efficacy of Adjuvant Tamoxifen for Early-Stage Breast Cancer

Tamoxifen remains the primary adjuvant endocrine option for premenopausal women with early-stage, ER-positive breast cancer. In this setting, there has been ongoing debate about whether the efficacy of tamoxifen to reduce risk for disease recurrence is affected by a patient's CPY2D6 status or by concentrations of endoxifen, the active metabolite of tamoxifen.

Now, investigators in the Netherlands have conducted a prospective, multicenter study (CYPTAM) study to associate CPY2D6 genotype and endoxifen concentration with relapse-free survival (RFS) in 667 patients with early-stage disease receiving adjuvant tamoxifen. Patients who switched from tamoxifen to an aromatase inhibitor during adjuvant treatment (approximately two thirds of the total) were censored from the analysis at the time of stopping tamoxifen.

At a median follow-up of 6.4 years, the median duration of tamoxifen therapy was 2.5 years. No association was found between CPY2D6 genotype and RFS or between endoxifen concentrations and RFS even when endoxifen concentrations were broken into quartiles. There was little information regarding the use of CPY2D6 inhibitors in the study (i.e., antidepressants), which conceivably could have biased the data, but the use of these agents in the Netherlands in this population is believed to be low.