Endocrine influences on human mammary cancer formationa critique

The possible relationship of abnormal C18 and C19 steroid excretions to fibrocystic disease and to carcinoma of the human female breast has been reviewed in relation to newer knowledge of estrogen receptor sites in uterine and mammary tissues. Proteins from these receptors exhibit different binding affinities for C18 and C19 steroids, with none of the latter exhibiting competitive binding. Within the C18 (estrogen) series, estriol inhibits competitively the uterotropic activity of estradiol 17B, displaces estradiol from uterine receptor proteins and thus far is not reported to be carcinogenic for the breast. Subnormal excretion of the C19 steriods androsterone and etiocholanolone relative to 17–hydroxycorticosteroids has been reported in chronic bronchial asthma and in untreated cancer of the breast but not thus far in premenopausal Caucasian women with fibrocystic mammary disease. Earlier reports of normal and increased estriol excretion in untreated mammary cancer compared with matched controls have not been confirmed by 3 recent investigations, in which fibrocystic disease alone, fibrocystic disease plus untreated mammary cancer and premenopausal or postmenopausal mammary cancer patients excreted subnormal estriol relative to estrone or estradiol. Hyperthyroidism is the only nonneoplastic syndrome reported thus far besides fibrocystic disease or cancer with reduced estriol quotients, but up to one fifth of euthyroid premenopausal women without mammary disease may excrete subnormal estriol quotients. Stress, tissue anoxia, ACTH therapy, pregnancy, hypothyroidism, obesity, castration and menopause normally increase the rate of estriol excretion relative to other estrogens and must be considered in future investigations needed to elucidate the divergent results reported for C18 steroid excretion in this disease.