The Evidence for an Endocrine Factor I N the Etiology of Mammary Tumors'

The endocrine origin of breast tumors rests on the hypothesis that the stimuli to normal growth, when active in increased intensity or applied over excessive or irregular periods of time, may result in atypical forms of proliferation. For that reason the facts of the hormone physiology of the normal mammary gland are of basic importance in the study of breast neoplasms. A . Experimental Physiology: The dependence of the normal growth and development of the female mammary gland upon the ovary is perhaps the central fact of breast physiology. I t was indicated first by castration and implantation experiments, and is now easily demonstrable by the injection of the estrogenic hormone into laboratory animals. That the mammary rudiments of male animals are likewise responsive to the ovary was also shown many years ago by implantation experiments, and the effect of the injection of estrogenic hormone on the male mammary gland of many animals is now well known. Recent reports of the enlargement of the breasts of women with a low or absent ovarian function following the injection of the estrogenic hormone (Werner and Collier, Loeser) add to the evidence that the human breast is also basically dependent on the ovary. It was first maintained that with the estrogenic hormone alone epithelial proliferation equal to that of pregnancy could be produced. Certain limitations and complications have, however, appeared. I n the first place, evidence has accumulated to show that a definite limit is reached (Vitemberger, Parkes, Turner and Frank) beyond which greatly increased amounts of estrin are incapable of producing a further physiologic effect. Other experiments suggest that estrogenic substances of different chemical composition act specifically on particular parts of the mammary gland. With certain compounds Burrows noted in mice an extension of the duct system with little development of acini, while with others the appearance of new acini was the prominent change. Similar experiments by Gardner, Smith and Strong showed that,