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20 1) Beatson, G. T.: On the treatment of inoperable case of carcinoma of the mamma, suggestion for a new method of treatment with. illustrative cases. Lancet, 18: , ) Humphrey, L. J. and Swerdlow, M.: The relationship of breast disease to thyroid disease. Cancer, 17: , ) Spencer, J. G. C.: Influence of thyroid in malignant disease. Brit. J. Cancer, 8: , ) Backwinkel, K and Jackson, A. S. Some features of breast cancer and thyroid deficiency. Cancer, 17: , ) Bogardus, G.M. and Finley, J. W. Breast cancer and tyyroid disease. Surgery, 49: , ) Eskin, B. A.: Iodine metabolism and breast cancer. Trans. N. Y. Acad. Sci., 32: , ) Lyons, A. R. and Edelsthyn, G. A.: Thyroid hormone as a prophylactic agent following radical treatment of breast cancer. Brit. J. Cancer, 19: , ) Lemon, H. M,: Cortisone-Thyroid therapy of metastatic mammary cancer. Ann. Int. Med., 46: , ) Edelstyn, G. A., Lyons, A. R. and Welbourn, R. B.: Thyroid function inpatients with mammary cancer, Lancet, 29: , ) Repert, R. W.: Breast carcinoma study; Relation to thyroid disease and diabetes. J. Mich. Med. Soc,, 51: , ) Carter, A. C. and Feldman, E. B.: Levels of serum protein-bound iodine in patients with metastatic carcinoma of the breast. J. Clin. Endocr. Metab., 20: , ) Dargent, M., Berger, M. and Lahneche, B.: La function thyroidienne chez les malades atteintes de cancer du rein. Acta Un. Int. Cancer., 18: , ) Reeve, T. S., Rundle, F. F., Hales, I. B. and Myhill, J.: Thyroid function in the presence of breast cancer. Lancet, 25: , 1961.

21 16) Dao, T., Bock,F.G. and Crouch, S.: Level of 3 Methylcholanthrene in mammary glands of rats after intragastric instillation of garcinogen. Proc. Soc. Exptl. Med., 102: , ) Flesher, J. W. and Sydnor, K. L.: Distribution and excretion of radioactivity in rats after oral administration of H3-3-Methylcholanthrene. Proc. Soc. Exptl. Biol. Med., 104: , ) Jull, J. W. and Huggins, C.: Influence of hyperthyroidism and of thyroidectomy on induced mammary cancer. Nature, 188: 73, ) Gruenstein, M., Meranze, D.R., Acuff, M. and Shimkin, M. B.: The role of the thyroid in hydrocarbon-induced mammary carcinogenesis in rats. Cancer Res., 28: , ) Newman, W. C. and Moon, R. C.: Chemically induced mammary cancer in rats with altered thyroid function. Cancer Res., 28: , ) Yokoro, K,, Imamura, N,, Takizawa, S, Nishihara, H. and Nishihara, E.: Leukemogenic and mammary tumorigenic effect of N-Nitrosobutyl-Urea in mice and rats. Gann, 62: , ) Reichin, S.: The effect of dehydration, starvation, and pitressin injection on thyroid activity in the rat. Rndocrinology, 60: , ) Mittra, I. and Hayward, J. L.: Hypothalamic-p ituitary thryo id axis in breast cancer. Lancet, 11: , ) Sinha, D., Cooper, D. and Dao, T. L.: The nature of estrogen and prolactin effect on mam mary tumorigenesis. Cancer Res., 33: , ) Salih, H., Brander, W., Glax, H. and Hobbs, J. R.: Prolactin dependence in human breast cancer. Lancet, 25: ) Franks, S., Palphs, D. N. L., Seagroatt, V. and JacJbs, H. S.: Prolactin concentration in patients with breast cancer. Brit. Med. J., 9: , ) Sinha, Y.N., Selby, R. W. and Vander Loan, W. R.: The natural history of prolactin and GH secretion in mice with high and low incidence of mammary tumor. Endocrinology, 94: , ) Mittra, I.: Mammotropic effect of prolactin enhanced by thyroidectomy. Nature, 248: , 1974.

22 Effects of thyroid function on breast cancer in rats and patients with breast diseases Nobuhiko KAJI The Second Department of Surgery, Okayama University Medical School, Okayama, Japan (Director: Prof. S.Teramoto) There are controversies over the influences of thyroid function on carciogenesis and progression of the breast cancer. To reveal the interrelation of the breast cancer and thyroid function in rats, this study was performed by employing N-nitrosobutylurea which is known for its carciogenetic action. Female Wistar rats were divided into 4 groups, namely, group with total thyroidectomy, group receiving thyroid sic (without thyroidectomy), group receiv ing thyroxin (without thyroidectomy), and control group. The thyroidectomy was done 14 weeks after birth and, thyroid sic and thyroxin started to be administered 14 weeks and 8 weeks after birth, respectively. Thyroid sic and thyroxin were given 0.5mg/day/rat and 10ƒÊg /100g body weight for 5 days in a week, respectively. N-nitrosobutylurea of 6mg/day/rat was administered to the rats of all the groups for 5 days in a week from the 6th post-natal week. In patients with various breast diseases functional levels of the thyroid gland were deter mined by measuring triiodothyroxine (T3 ), Thyroxin-binding-globulin (TBG), thyroid-stimulat ing-hormone (TSH) and prolactin. Blood samples were obtained in early morning and, serum samples obtained were frozen and stored. T3, TSH and prolactin were measured by radio immunoassay, triosorb test by resin-sponge uptake method and TBG by electrophoresis with cellulose acetate membrane. The patients studied consisted of 8 with fibroadenoma mammae, 4 with mastopathy and 52 with breast cancer. Results obtained in the study are as follows: 1) Carciogenetic action of N-nitrosobutylurea in rats with total thyroidectomy was greater at the beginning of the administration, but long-term administration of N-nitrosobutyl reduced its carciogenetic effect. 2) There was no carciogenetic influence in NBU on rats with thyroid sic administration. 3) No carciogenetic effect was found in rats with subcutaneous administration of thyroxin. 4) TSH and PRL were higher in patients with breast cancer, particularly in earlier stage, compared with those in patients with benign breast diseases, including mastopathy and fibro adenoma mammae. However, there was no correlation of TSH and PRL levels to stages of the breast cancer. 5) PRL was elevated after radical mastectomy than that before the operation. 6) There was no significant difference in T3, triosorb test and TBG between patients with the benign diseases and those with breast cancer.

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