Vietnamese and Chinese women with hormone receptor-positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen.

BackgroundWhile tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results.FindingsIn an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case–control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease.We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control.ConclusionsThis exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70 ng.ml), endoxifen may promote recurrence.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-52) contains supplementary material, which is available to authorized users.

In premenopausal women with operable breast cancer not selected for estrogen receptor status or with estrogen receptor-positive tumors, 5- and 10-year DFS and OS rates are significantly improved following adjuvant oophorectomy and tamoxifen.

The phase of the menstrual cycle at which surgery was done had no impact on survival for women who received mastectomy only. However, women who received a mastectomy and surgical oophorectomy and tamoxifen during the luteal phase had better outcomes than women who received surgery during the follicular phase.

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