Response: Re: Combined Treatment With Buserelin and Tamoxifen in Premenopausal Metastatic Breast Cancer: a Randomized Study

Extract

In his correspondence, Powles wonders why an increased rate of response during combined endocrine therapy in both of our trials was followed by statistically significantly improved survival in our European Organization for Research on Treatment of Cancer study (1), but not in his study (2), when compared with single tamoxifen treatment. Indeed, both trials are “similar” with respect to one of the main objectives of the studies (i.e., testing the hypothesis that combining estrogen deprivation with estrogen receptor [ER] blockade is clinically superior to ER blockade by tamoxifen alone). However, there are many differences between the two trials, such as menopausal and associated endocrine status, duration of follow-up, distribution of steroid receptor subgroups, pretreatment, doses of tamoxifen, and pharmacologic interaction between the different agents combined.

In our study, tamoxifen strongly increased plasma estradiol levels in premenopausal patients in contrast to what happens in postmenopausal women, as shown in the study by Powles et al. (2). In this respect, we disagree with the statement of Dr. Davidson in her excellent editorial (3) that our study suggests that the divergent effects of tamoxifen and the luteinizing hormone-releasing hormone (LHRH) agonist buserelin on the level of serum 17β-estradiol are not clinically significant because there was no major difference in clinical outcomes for the tamoxifen or buserelin groups. We think that the strongly increased estradiol levels induced by tamoxifen indeed had a deleterious effect by competition with tamoxifen for the binding to ER and that, consequently, estrogen suppression by adding buserelin to tamoxifen treatment (resulting in postmenopausal estrogen levels) statistically significantly increased the antitumor efficacy of tamoxifen as shown by our data.