Endocrine status of premenopausal node-positive breast cancer patients following adjuvant chemotherapy and long-term tamoxifen.

The endocrine status of 49 premenopausal women taking tamoxifen after completion of adjuvant chemotherapy for breast cancer was determined by radioimmunoassay from serial blood samples. Of these 49 women, 7 had regular menses, 14 had irregular menses, 23 were amenorrheic, and 5 had undergone hysterectomies. A group of 12 premenopausal women who had no history of breast cancer and were not taking tamoxifen served as a control group. Evidence of ovarian function (estradiol levels of greater than 100 pg/ml) was seen in 7 of 7, 9 of 14, 2 of 23, and 1 of 5 women with a clinical history of regular menses, irregular menses, amenorrhea, and hysterectomy, respectively. Supraphysiological levels of estradiol (greater than 350 pg/ml) were noted in 13 of 19 women with endocrine evidence of ovarian function. Supraphysiological progesterone levels (greater than 20 ng/ml) were also seen in 5 of 7 of the regularly menstruating women taking tamoxifen. Supraphysiological levels of estradiol were associated with elevated follicle-stimulating hormone levels, but there was no mean change in the luteinizing hormone levels. Minimum and maximum serum follicle-stimulating hormone levels were 1.9 and 9.0 mIU/ml in the 12 normal women and 5.2 and 24.3 mIU in the 13 women with supraphysiological estradiol levels. Our findings demonstrate that the majority of women who continue to menstruate while taking continuous tamoxifen following cytotoxic chemotherapy have supraphysiologic estradiol levels. This is a potential mechanism for failure of tamoxifen therapy in these premenopausal women.