The production of mammary cancer in rats using oestrogens.

Abstract

An attempt to confirm previous observations that mammary cancer can be induced in rats by prolonged stimulation with estrogenic substances and to determine any variation in the response of different strains of rats to the carcinogenic action of estrogens on their mammary glands is presented. The results while confirming the previous reports varied with the strain of rats employed. A strain of albino rats used had been randomly bred over many years without a single case of malignant breast tumor developing. Another strain of albino rats used (WAG rats) had been maintained by brother-to-sister mating for about 50 generations. Spontaneous mammary cancers had been very rare. Black and white rats formed the 3rd group used. Although many of the older females had developed benign mammary tumors only occasionally had a mammary carcinoma been found. The estrogens used - estradiol estradiol dipropionate and stilbestrol - were implanted as pellets of 5-6 mg each. Each rat was implanted with 2 pellets of the same substance 1 at the age of 4 weeks and the other 1-3 months later. All animals were observed until they died. At death postmortem examinations were made of all organs. There was no evidence of tumor production at implantation sites. The total number of female animals used was 140. Estradiol or its dipropionate resulted in marked retardation of growth loss of activity partial loss of hair and ataxic symptoms. Stilbestrol showed less difference in weight compared with controls but no other symptoms except slight ataxia. Estradiol and the dipropionate produced similar findings. The main effect on the breast tissue was 1 of atrophy. There was also cyst formation with minimal stromal reaction. Occasionally the cellular appearance was that of a premalignant change. There were 18 rats with malignant breast tumors. In 8 of them there were multiple tumors. These were adenocarcinoma papillary carcinoma and anaplastic carcinoma. Squamous metaplasia was not seen. No tumors were found in control rats of the WAG and other albino group. Among the black and white strain there were 5 benign breast tumors. Enlargement of the pituitary gland was a consistent finding in all experimental animals. Cystic ovaries were frequent. In those implanted with stilbestrol there were 2 malignant ovarian tumors and 2 of uterine origin. Of a total of 140 female animals of 3 strains treated with estrogens 21 had developed malignant mammary tumors and 4 had malignant tumors of the ovaries or uterus.