Effects of tamoxifen on steroid hormone receptors and hormone concentration and the results of DNA analysis by flow cytometry in endometrial carcinoma

Objectives. Tamoxifen is a nonsteroidal triphenylethylene derivate with a p redominant antiestrogen activity, used in the endocrine treatment of breast and endometrial cancer. It is not known which endometrial carcinomas will respond favorably to tamoxifen and which ones will not. The aim of this stu dy was to find out whether tamoxifen has an effect on hormone steroid recep tors, hormone concentration, DNA content, and proliferative activity in end ometrial cancer and to correlate the tamoxifen-induced changes with patholo gic parameters such as clinical stage, tumor differentiation, depth of inva sion, and histologic type. Methods. Thirty postmenopausal women with endometrial carcinoma were treate d with 30 mg of tamoxifen daily for 7-10 days after curettage. Steroid horm one receptors (estrogen and progesterone receptors), levels of follicle-sti mulating hormone, luteinizing hormone, prolactin, estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and DNA ploidy and proliferative activity were determined before and after therapy. The patients were also divided into favorable and unfavorable pro gnosis groups according to classical histological parameters. The patients in the favorable group consisted of patients with stage I disease, well and moderately differentiated tumors, favorable histologic type, and a depth o f myometrial invasion of less than 1/3. The patients with only one of the u nfavorable parameters (clinical stage II or III, poorly differentiated tumo rs, unfavorable histologic types, and deeper invasion of myometrium) were i ncluded in the unfavorable prognosis group. Results. After the treatment, there was a net increase in the progesterone receptors and sex hormone binding globulin and a significant decrease in th e estrogen receptors. The increase in progesterone receptors and decrease i n estrogen receptors occurred in the patient group with favorable prognosis regarding histologic type, degree of differentiation, and clinical stage, but also in the unfavorable prognosis group regarding the depth of myometri al invasion. Statistically significant decrease in the follicle-stimulating hormone concentration was observed in the groups with favorable prognosis regarding histologic type, depth of myometrial invasion, and grade of diffe rentiation. Concentration of sex hormone binding globulin was significantly increased in groups with favorable prognosis if histologic type and grade of differentiation were taken into account. On the other hand, there was a significant decrease in the concentration of luteinizing hormone in the gro up with unfavorable histologic type and also a decrease in progesterone con centration in patients with unfavorable prognosis regarding the grade of di fferentiation. There was no statistical significance either in the concentr ations of other hormones measured or in the DNA analysis by flow cytometry. Conclusions. Our results revealed that tamoxifen can increase progesterone receptors and decrease estrogen receptors in endometrial cancer. The effect was most pronounced in tumors with favorable clinicopathologic parameters. We conclude that tamoxifen therapy can induce progesterone receptor synthe sis even in tumors with low initial progesterone receptor levels, making su ch tumors potentially responsive to additional hormonal therapy with proges terone. (C) 1999 Academic Press.