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Pituitary Function and Hormonal Therapy of Experimental Breast Cancer¹

( Department of Pathology, Roswell Park Memorial Institute, Buffalo, New York)

The effects of estrogen, ovariectomy, adrenalectomy, progesterone, a combination of progesterone with estrogen, androgen, and a combination of androgen with estrogen on a hormone-responsive mammary adenocarcinoma and on the female host rats were analyzed with respect to the function of the anterior pituitary gland. These effects were, notably, changes in the body weight, anterior pituitary gland, ovaries, uterine horns, adrenals, thyroid, thymus, and mammary glands. Experimental and clinical studies by others were also surveyed to establish the mode of action of gonadal hormones in the control of breast cancer. It is concluded that stimulation or inhibition of the growth of a hormone-responsive breast cancer is roughly reflected on the plasma prolactin levels of the tumor host. In addition, however, although the effect of the 3 gonadal steroids on the host mammary gland is mediated by the pituitary, these steroids also appear to have a direct influence on the growth of the tumor, which is slight but significant. With estrogen, larger doses are more inhibitory but with androgen, smaller doses are more effective in retardation of the tumor growth. The combination of progesterone with estrogen is stimulatory, and this growth-enhancing effect on the tumor greatly increases in the absence of the pituitary gland. The combination of a large dose of estrogen with a small dose of androgen is more effective in the control of breast cancer than either one alone. For adrenalectomy to be effective in retardation of breast cancer, a complete suppression or absence of ovarian function is necessary.

¹ The studies quoted in this paper were mostly carried out under the direction of Dr. J. Furth at Francis Delafield Hospital, Division of Columbia University, and aided in part by Contract PH32-63-106 from the Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, by a general research support grant, NIH, and by a grant from the Hartford Foundation.