This was a newly recognized property of mammary cancer in experimental animals. Many of the established mammary cancers underwent a considerable diminution in size or disappeared after appropriate hormonal modifications of the host (Figs. 14, 15). Some of the methods effective in this regard were (1) ovariectomy, (2) hypophysectomy, or (3) administration of dihydrotestosterone. Less frequendy, these same hormonal modifications failed to cause regression of the carcinoma and the characteristic atrophy was not observed.

The mammary cancers which diminished in size after the effective hormonal modifications exhibited thereafter a characteristic cytologic appearance of atrophy (or a disappearance of the malignant epithelial cells) which was characteristic in all groups. The erstwhile tumor acini were still surrounded by myo-epithelial cells, but their many layers of plump epithelial cells were replaced by a single row of flat cells (Fig. 13); in some cases the carcinoma cells disappeared entirely. The tumors which did not decrease in size after the hormonal modifications contained acini lined with many layers of epithelial cells.

In certain tumors there was evidence that some of the cells had undergone hormone-withdrawal atrophy, while other cells were hormone-independent in character. In growths of this sort, some areas of the tumor consisted of atrophic acini, whereas adjacent acini were lined by many layers of cancer cells. Clearly, the cell population of these tumors was not uniform in its functional or morphologic response to ovariectomy. Hormone-dependence or independence, respectively, is a function of the tumor and not of the host (46).

Hormone-dependent mammary cancers regress after ovariectomy. It was found that ovariectomy induced in tumors of this class a decline in the levels of (a) respiration, (b) glucose-6-phosphate dehydrogenase, (c) 6-phosphogluconic dehydrogenase, and (d) lactic dehydrogenase. There was no great change in the level of isocitric dehydrogenase, while the level of malic enzyme (TPN) was doubled.

Hormone-independent tumors did not regress after ovariectomy. In tumors of this class, it was observed that ovariectomy resulted in decline only in levels of (a) glucose-6-phosphate dehydrogenase and (b) malic dehydrogenase (DPN); the level of lactic dehydrogenase was increased.