A Review of the Evidence Linking Estrogens and Cancer in Animals

¹ Departments of Pharmacology and Obstetrics and Gynecology, George Washington University Medical School, Washington, D.C.

This Conference has involved a very highly qualified treatment of the biochemical, clinical, and epidemiological aspects of the estrogen-cancer problem. Accordingly, I have assumed that it is my assignment to cover the experimental biological facets of this problem. This I shall endeavor to do with a major emphasis on the historical development of our knowledge in this field.

It is instructive to examine the very early experimental observations that initially raised the question of the role of steroid hormones in the etiology and pathogenesis of cancer in the recognized target organs.

Almost at the very beginning of modern endocrinology, Allen and Doisy¹ reported the cornification of the vaginal epithelium of the mouse following administration of ovarian extracts. They appreciated that this represented a remarkably active tissue proliferation requiring a degree of mitotic activity seldom seen in normal tissues. Thus, Allen et al.² actually used colchicine to arrest the mitotic activity induced by estrogen in the vaginal mucosa and in the myometrium of the rat. They reported that a transverse section of the vagina at 37 hours after a single injection of estrogen contained as many as 1,585 mitoses. Equal mitotic activity was also reported for the estrogen-treated uterus.³ These observations provided the experimentalist with a potent growth-stimulating agent that profoundly affected the female genital tract, so commonly the site of cancer in women.

These findings arose against a background of both experimental and clinical knowledge of the relationships of ovarian function to the pathogenesis of breast cancer, for Beatson⁴ had shown as early as 1898 that ovariectomy ameliorated the clinical course of breast cancer in women.