Kwapien R P, Giles R C, Geil R G, Casey H W
J Natl Cancer Inst. 1980 Jul;65(1):137-44.
Of 172 beagle dogs administered investigational oral contraceptive steroids for 2.4-5.2 years, 9 developed malignant mammary tumors. At necropsy their ages varied from 41 to 70 months, with a mean age of 4.9 years. The malignant tumors were observed in 1 dog that received ethynerone plus mestranol at 1.05 mg/kg/day and in 4 dogs that received chlorethynyl norgestrel plus mestranol at 1.05 mg/kg/day. Also, 4 dogs that received anagestone acetate plus mestranol at either 0.44 or 1.10 mg/kg/day developed malignant mammary tumors. Malignant tumors were not seen in 33 dogs administered mestranol at 0.02 and 0.05 mg/kg/day for 7 years or in 18 dogs given ethynerone without mestranol at 1.00 mg/kg/day for 5 years. No malignant tumors were observed in 18 control dogs maintained for 7 years without treatment. Three dogs had single malignant mammary nodules, 3 dogs had 2 malignant nodules, 2 dogs had 4-6 malignant nodules, and 1 dog in the treatment group given high dosages of ethynerone plus mestranol had 14 mammary nodules composed of fibrosarcoma. The malignant tumors were histologically classified as 5 anaplastic carcinomas, 2 solid carcinomas, 1 tubular adenocarcinoma, 1 squamous cell carcinoma, and 1 fibrosarcoma. Most dogs had only 1 histologic type of cancer (8/9 dogs); however, 1 dog had carcinomas of both solid and anaplastic types involving different glands. Metastases were present in 5 dogs and most often involved regional lymph nodes and lung.
