Anterior pituitary function in patients with advanced breast cancer in reference to bilateral total adrenalectomy and oophorectomy

Abstract

For decades it has been postulated that hormonal inbalance is a major factor in tumorigenesis in the target organ. The regression of breast cancer induced by oophorectomy has been attributed to the removal of ovarian hormones in which estrogens play a important role. It is also known that the adrenal cortex secrete an amount of estrogen. These findings led to the conclusion that oophorectomy and adrenalectomy should be recommended for advanced breast cancer in man. In addition, there are extensive experimental data suggesting that pituitary hormones also lead to mammary tumors.Recently, it has been established that adrenalectomy and oophorectomy, or hypophysectomy can induce prolonged regression of advanced breast cancer in 50 percent of patients. About 50 patients with advanced breast cancer received bilateral total adrenalectomy and oophorectomy in our clinic, 50 per-cent of these patients had remissions during more than 1 month and 40 per cent during more than 6 months. The average period of remission was 13.4 months. This operative procedure was effective because the mean survival time of remitted patients was 20.3 months compared with 2.3 months in non-remitted patients. Nearly half of the patients thus treated were benefited however, the rest had no remission.If the effectiveness of this procedure could be predicted for each patient, unncessary major surgery would be avoided for those patients who obtained no remission. Moreover, even among remitted patients who had a relapse after one year or so, the exact mechanism of the relapse remains obscure.The purpose of this paper is to put forward a working hypothesis in the hope that further investigation may lead to an anticipation of the effectiveness of surgery and an understanding of the exact mechanism of relapse. Several anterior pituitary functions before and after bilateral total adrenalectomy and oophorectomy were studied.Urinary excretion of prolactin was determined by pigeon crop-sac method, urinary excretion of gonadotrophin was determined by chemical assay and bio-assay (mouse uterine weight method), serum sulfation factor was determined by ALMQVIST's method, and blood ACTH activity was estimated by adrenal ascorbic acid depletion method in hypophysectomized rat.The summary of results was as followed : 1) No increase of excretion of prolactin, gonadotrophin and growth hormone was observed in patients with breast cancer. 2) No excess excretion of ACTH was observed in the adrectomized and oophorectomized patients with advanced breast cancer when they were maintained with adequate administration of steroid. No increase of excretion of prolactin, gonadotrophin and growth hormone was also observed in these patients.3) There was no correlation between efficiency of surgery and the urinary excretion of prolactin and gonadotrophin. Therefore, it was impossible to anticipate the response of adrenalectomy and oophorectomy.4) No increase of excretion of prolactin, gonadotrophin and ACTH was observed in the relapsed patients who previously had remissions after adrenalectomy and oophorectomy. It may be concluded that there are some other factors influencing the relapse besides pituitary hormones.