The earliest indication that regression of advanced cancer in living creatures can be effected was derived from removal of normal organs, namely, the ovaries of women

cancer in living creatures can be effected was derived from removal of normal organs, namely, the ovaries of women (2). This empiric therapeutic procedure was remarkable insofar as it was made before there was any concept of endocrine action. Following this discovery, Lathrop and Loeb (32) found that removal of ovaries prevented onset of mammary cancer in a considerable number of mice. Lacassagne (30) was the first to show that a correlation exists between development of cancer and hormones, since a steroid with estrogenic activity incited formation of mammary cancer; in a famous experiment weekly injections of 30 @gof estrone benzoate evoked cancer of the breast in each of 3 male mice in 5—6months. The proof that modification of hormonal status can cause regression of cancer came from a study of tumors of canine prostate (15) : injection of stilbestrol resulted in a profound decrease in size of benign and malignant pros tatic tumors, even those of huge size, in the dog. The hormonal control of cancer applied to far advanced carcinoma of the prostate in man (21). It was found that testosterone accelerated the growth of human prostatic cancer, whereas, in contrast, orchiectomy or the injection of estradiol benzoate or of stilbestrol caused in most patients a dramatic and long-lasting regression of their cancers. Stilbestrol was the first synthetic substance found to be an anti-cancer drug. There are 2 principles in the destruction of cancer cells in living creatures by modifications of endocrine status: (a), hormone deprival; (b) hormone interference in the cancer cell. Malignant cells can regress from too little or too much hormone. Hormone interference causes severe damage or death of cancer through toxicity in the carwer cell while normal cells are relatively undamaged. Not all cancers that regress from hormone deprival also regress from excessive amounts of the same hormones.