Lawrence and Tobias (S3) have investigated the effects of external radiation (a beam of protons derived from the cyclotron) of the hypophysis in mammary cancer. While some decrease of function of the target organs was observed, the effects on cancer of the breast have not yet been fully evaluated.

Administration Of Phenolic Estrogens

There is evidence that phenolic estrogens have an ameliorative effect on certain patients with mammary cancer. A paradox is involved in the treatment of breast cancer with estrogens, since compounds in this class are believed to be activating agents in many cases of mammary cancer; indeed, one of the purposes of adrenalectomy and ovariectomy is the elimination of endogenous estrogens. The paradox may be explained on the basis of the quantities of the estrogenic phenols which are involved. It has been shown that phenolic estrogens have a bi-phasic effect (29) on the growth of mammary tumors in ovariectomized rats; small amounts of phenolic estrogens promote the growth of this benign tumor, while large quantities block its growth.

The administration of phenolic estrogens to women with mammary cancer was introduced by Haddow et al. (9). The rationale underlying the investigation was the fact that many carcinogenic polycyclic hydrocarbons possess the property of retarding the growth both of normal and malignant cells. It had also been established before this study that phenolic estrogens retard the growth of human prostatic carcinomas.

Administration Of Testosterone

It is certain that treatment with certain members of the androstane series causes regression of the tumor in certain women with advanced mammary cancer.

In 1939 Loeser (34) presented evidence that testosterone delayed recurrence following radical mastectomy for cancer of the breast. In December, 1941, Loeser (35) confirmed his earlier impression and extended his observations to include temporary improvement in women with metastatic mammary cancer.

The mechanism of action of testosterone in causing regression of mammary cancer is unknown. Myers et al. (38) observed that testosterone caused exacerbation of metastatic mammary cancer in bone in certain women; this stimulatory effect was related to the conversion of testosterone to estrone and estradiol.

Leukemia

It is known that cortisone and related steroids will cause a remission in acute leukemia and in certain chronic lymphogenous tumors.

Dougherty and White (5) had observed that increased adrenal cortical function resulted in involution of normal lymphoid tissues. Heilman and Kendall (11) discovered that cortisone caused a rapid, profound yet temporary regression of a transplanted lymphosarcoma in mice; furthermore, when injections of this steroid were begun soon after inoculation of the tumor, its growth was delayed as long as cortisone was administered. Pearson et al. (41) observed that ACTH or cortisone resulted in a temporary regression in the size of enlarged lymph nodes in chronic lymphatic leukemia and Hodgkin's disease. Likewise, these agents induce a profound remission (42) in about 50 per cent of children with acute leukemia. The remissions in acute leukemia, while impressive, last for a few weeks or months only.

Comment

The origin of treatment of cancers of man through changes in his steroid environment has been traced in this paper. The principal experimental pathways leading to these concepts have been the biochemistry and physiology of normal cells, while laboratory studies utilizing malignant cells as test objects have had only a small influence in this regard. Yet it cannot be doubted-indeed, it is self-evident-that the study of neoplastic cells is the central problem of cancer research. The development of laboratory methods to study the effect of hormones on neoplastic cells is a problem for the present. It may be pointed out that many hundreds of steroids have been synthesized but have never been examined for their effects on the promotion or restraint of growth.

References

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