Hormonal influences on mammary tumors of the rat. I. Acceleration of growth of transplanted fibroadenoma in ovariectomized and hypophysectomized rats.

A transplanted mammary fibroadenoma was found to grow in 95 per cent of intact adult female rats and the increment of tumor weights was progressive and logarithmic. The growth of the tumor was retarded by ovariectomy and still more when this was combined with adrenalectomy. In ovariectomized rats the growth of the tumor was stimulated by phenolic estrogens, this increase being enhanced when progesterone was added. In these responses to hormonal changes the mammary gland and the tumor resembled each other. Yet there are many differences between the growth of the fibroadenoma and that of the mammary gland. In contrast to the progressive growth which occurred in intact adult females there was a prolonged period of indolent growth of transplants in hypophysectomized rats; but after many weeks active growth began and the tumors eventually reached large size. During the period of quiescent growth the tumor was cytologically atrophic but after the growth spurt had started the microscopic appearance of the fibroadenoma resembled that of tumors growing in normal adult females. The mammary gland remained atrophic during both the slow and the accelerated phases of tumor growth, and so too with the other secondary sex expressions. In hypophysectomized rats estrone and progesterone, when combined, stimulated the growth of the tumor, and this growth was accelerated by the additional administration of lactogenic or growth hormones. None of these hormones, separately, stimulated the growth of the tumor. In ovariectomized rats other differences were demonstrated between the growth of the mammary gland and the fibroadenoma. Progesterone, injected alone, accelerated the growth of the tumor but not that of the mammary glands. The administration of phenolic estrogens exerted a biphasic effect on the growth of the tumor whilst that on the breast of its hosts was monophasic. With progressively increasing doses of these phenols there occurred primarily an augmentation of the rate of growth of the tumor until a peak was achieved; an increase of the dose above the optimal amount depressed the growth of the tumor. The stage of depression of growth was not observed in the mammary glands of these tumor-bearing rats. Many steroids which induced gestational changes in the mammary gland accelerated the growth of the tumor. Among these were estrone and progesterone in combination and 17alpha-ethinyl-19-nor-testosterone administered alone. But gestational changes developed in the mammary gland of rats treated with 4-androstene-3alpha,17beta-diol, without growth of the tumor. The evidence which we have presented proves that the mammary fibroadenoma tested had some of the functional properties of a normal mammary gland, and neoplastic traits as well. In its response to hormones it had characteristics which set it apart from all other endocrine targets of the rat.