Prolactin and breast carcinoma.

Abstract

The recent findings regarding the possible relation of prolactin to human breast cancer are reviewed. Prolactin is a single-chain polypeptide hormone secreted by the anterior pituitary; it appears important to the development and growth of mammary tumors in mice and rats. Certain drugs (L-dopa, the ergot derivatives) inhibit the release of prolactin from the anterior pituitary and lower its serum concentration. Chlorpromazine and other phenothiazines block the synthesis, release, or action of prolactin-inhibiting factors leading to increased prolactin secretion. The midcycle serum estrogen elevation does not increase serum prolactin but often high doses of estrogen will. Mammary tumors in mice and rats appear different from those in human, being of alveolar origin while human tumors are thought to be ductal. Also, rodent cancers do not usually metastasize, even when large. About 40% of human breast cancers respond to endocrine therapy while in Sprague-Dawley rats induced mammary tumors are 80% hormone responsive. In mice hyperplastic nodules but not mammary cancers respond to horomone deprivation. Prolactin is a key hormone in the stimulation of hyperplastic nodules in mice and mammary tumors in rats. The effects of progesterone on these growths is not clear. Serum prolactin levels normally vary throughout the day. Levels are not different in cancer patients but certain families with high cancer rates have been shown to have higher than normal serum levels. Although prolactin receptors have been identified in mouse and rat mammary tissue and tumors and prolactin responsiveness of the tumors correlated with the number of such receptors, these receptors have not been identified in human breast cancer cells. Patients have responded to L-dopa with relief of bone pain and a 50% decrease in serum prolactin. Suppressing atypical precancerous lesions by depriving them of their hormonal support offers the best chance for preventing eventual development of breast cancer. In vitro determination of the presence of prolactin receptors in human breast tumor tissue may allow accurate prediction of response to endocrine ablation. Variations in prolactin receptors may account for response differences of breast tumors to different doses of estrogen. Near-zero prolactin levels following hypophysectomy in some patients have been correlated with clinical remissions. Combinations of drugs to reduce serum prolactin levels or antagonize the hormones's effect on the breast may be needed to obtain results.