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Excretion Patterns of Urinary Metabolites of Estradiol-4-C¹⁴ in Postmenopausal Women with Benign and Malignant Disease of the Breast¹

(From the Departments of Surgery, Biochemistry, and Pathology, University of Southern California School of Medicine, and the Tumor Surgical Service of the Los Angeles County General Hospital)

A study of the excretion patterns of the urinary metabolites of estradiol-4-C¹⁴ administered to a group of 43 postmenopausal women, 38 with advanced mammary carcinoma prior to endocrine therapy and 5 with benign mammary dysplasia, is reported. A chromatographic method was employed for the determination of estradiol, estrone, and estriol and other estrogen metabolites. The urinary excretion pattern is defined by (a) the extent of excretion of isotope in each of 3 successive 24-hr. collection periods, (b) the percentage of the urinary radiometabolites enzymatically hydrolyzed, (c) the relative concentration of the several metabolites in the hydrolyzed fraction. Wide subject-to-subject variations were found. The metabolites other than estradiol, estrone, and estriol comprised a large portion of the total estrogens excreted. A significantly lower amount of estradiol was noted in the group of women with mammary carcinoma as compared to the amount found in the group of women with benign mammary dysplasia, suggesting that the former group metabolizes more rapidly the administered estradiol. Although the excretion patterns of patients who failed to respond to estrogen treatment (nonresponders) differed the greatest from the patterns associated with benign disease, distinctive patterns of the urinary excretion of isotopic estrogens which allowed a statistically significant or clinically useful separation between responders and nonresponders to subsequent estrogen therapy were not discovered.

¹ This work was supported in part by grant CA-02489 from the USPHS. Preliminary reports of a part of these findings were presented at the American Association for Cancer Research, 1960 (14), the First International Congress of Endocrinology, 1960 (12), and at the meeting of the American College of Surgeons, Southern California Branch, 1962.

² Present address: Department of Surgery, Stanford University School of Medicine.

Received 6/ 3/64. Revised 11/ 9/64.