Effects of Tamoxifen Adjuvant Therapy and a Low-Fat Diet on Serum Binding Proteins and Est radio l Bionvailabi lity in Postmenopausal Breast Cancer Patients1

Serum was collected at intervals from postmenopausal breast cancer patients to determine the effects of tamoxifen adjuvant therapy and a low-fat dietary intervention, alone and in combination, on sex hormonebinding globulin (SHBG) concentrations and circulating estradici bioavailability. Serum corticosteroid-binding globulin and follicle-stimulat ing hormone were also assayed as indicators of patient compliance to tamoxifen therapy. The immunoreactive SHBG concentration was higher (/' < 0.001) in 22 patients who had been treated with tamoxifen for 6-36 weeks when first sampled, compared with 27 who were not receiving tamoxifen therapy. Tamoxifen also produced a reduction in the percentage non-protein-bound estradiol (/' < 0.001) and percentage albumin-bound estradiol (P < 0.01), the two biologically available frac tions, and a corresponding increase in the percentage SHBG-bound estradiol (/' < 0.01). A longitudinal study of 7 patients showed signifi cant reductions in the percentage of albumin-bound estradiol and an increased percentage of SHBG-bound estradiol, after 3-6 months of tamoxifen; after 12-18 months there was also a significant decrease in the non-protein-bound estradiol fraction. We conclude that in postmeno pausal breast cancer patients the redistribution of circulating estradiol, with reduced bioavailability, provides an additional mechanism to those demonstrated previously for the therapeutic activity of tamoxifen. Another 12 patients receiving tamoxifen and 8 who were not were followed for 6-12 months on a low-fat diet (fat comprised 20% of the total calories). The dietary intervention had no effect on the serum SHBG concentration or the estradiol distribution. Although tamoxifen increased the serum corticosteroid-binding glob ulin and partially suppressed the follicle-stimulating hormone concen trations, the responses obtained were less consistent compared with those of the SHBG levels.