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.