The Constitutional Factor I N the Incidence of Mammary Tumors

The object of the present communication is to establish the fact that, in a mammal which has long been subjected to intensive and extensive laboratory investigations, constitutional factors are normally of prime importance in determining whether or not the individual organism will form a mammary tumor. In addition, constitutional factors may also play an important part in determining what general type of mammary tumor is formed. The material used is mice. I t may be well, at the outset, to emphasize the fact that the type of mammary tumor to which reference is ordinarily made in this paper is the common adenoma-carcinoma series in which the epithelial elements are definitely the site of the most pronounced neoplastic development. The distinction between this group and that in which the connective tissue is most active is brought out by a comparison of the incidence of the two types in a reciprocal outcross between two inbred strains, reported by Murray and Little (1935). Cloudman has completed the histological diagnosis of each tumor tabulated. In one outcross (dBF, and F,) using females of high mammary tumor stock, there was a total of 239 adenomas and carcinomas, with 4 fibrosarcomas. The percentage of fibrosarcomas is 1.6. In the reciprocal cross (BdF, and F,) using females of low mammary tumor stock, among 30 tumors, mammary in position, 9 or 30.0 per cent were fibrosarcomas. The influence of constitution on the incidence of the two types is striking. Long ago Tyzzer, J. A. Murray, Bashford and others showed that mammary tumors occurred much more frequently among the descendants of tumorforming ancestors than they did among the descendants of mice which did not form mammary tumors. These earlier writers spoke of high-tumor families or strains as contrasted with low-tumor families or strains and expressed their belief that there were constitutional differences at the basis of the distinction between the two groups. Slye, in a long series of papers, included mammary tumors in her general conclusion that the tendency to form cancer was definitely inherited as a mendelian recessive. Regardless of whether her genetic interpretation was correct, all her data, as well as the data of Lathrop and Loeb, as analyzed statistically by Bernstein, showed that constitutional differences in different lines of descent were the simplest and most consistent explanation for the results obtained, From the point of view of genetics, all of this work left a great deal to be desired because none of the investigators had established, by close inbreeding,