Antimammary carcinogenic activity of 17‐alpha‐ethinyl estriol

• Published in: Cancer Vol. 60; no. 12; pp. 2873 - 2881
• Main Author: Lemon, Henry M.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 15.12.1987; Wiley-Liss
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - antagonists & inhibitors; Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - antagonists & inhibitors; Chemical agents; Ethinyl Estradiol - therapeutic use; Female; Mammary Neoplasms, Experimental - chemically induced; Mammary Neoplasms, Experimental - prevention & control; Medical sciences; Rats; Time Factors; Tumors; Vertebrata; Chemotherapy; Mammalia; Rat; Animal; Rodentia; Estrogen; Mammary gland; Anticarcinogen; Experimental tumor
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19871215)60:12<2873::AID-CNCR2820601204>3.0.CO;2-B

Both initiation and promotion of dimethylbenz(a)anthracene (DMBA)‐induced mammary carcinogenesis were inhibited by prophylactic therapy for 1 to 7 months using 17‐alpha‐ethinyl‐estriol in doses as low as 1.0 μg/d administered to intact virgin female Sprague‐Dawley rats at 35 to 65 days of age. Administration of 638‐μg single or multiple doses 2 to 3 weeks before DMBA induced a 75% to 85% reduction in cancer incidence after 1 year (P < 0.001). When treatment was begun 2 weeks after DMBA, 1.0 μg/d infused for 84 days resulted in a 44% reduction in incidence, with higher‐dose, more prolonged therapy achieving a 73% reduction, equal to the reduction in carcinoma incidence observed after ovariectomy. Biopsies of nontumorous mammary glands showed a positive correlation between prelactational lobuloalveolar hyperplasia, hormone dose, and reduction in incidence of mammary carcinoma. Similar treatment with 17‐alpha‐ethinyl‐estradiol‐17B and diethylstilbestrol did not inhibit the 90% to 100% incidence of carcinoma observed in DMBA‐treated control rats, and induced lactational hyperplasia in mammary gland biopsies. Continuous ethinyl estriol infusion subcutaneous (sc) in 2.5 to 7.5 μg daily dosage significantly increased uterine weights by as much as 10% to 46% after 2 to 4 weeks. At the time of mammary neoplasm development when rats were necropsied, no significant difference was observed in uterine weights between rats receiving 638 μg/mo in a readily soluble pellet implant, and uterine weights of control rats. Ethinyl estriol given seven times monthly in 638‐μg bolus doses was more inhibitory of mammary carcinogenesis than estriol after a year (P < 0.1 > 0.05). Short‐term intermittent administration of ethinyl estriol to young nulliparous women may offer a method of simulating the differentiating effect of pregnancy on mammary tissues, increasing durable resistance to carcinogenesis.