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The particular patterns of familial aggregations of cancer in the several families reported from our clinical resource suggest that multiple genotypes explain their diversity of cancer susceptibility. This knowledge could be of value in improving cancer control. We postulate that each particular genotype functions in concert with differential carcinogenic interactions, including a possible oncogenic virus, contributing to carcinogenesis in the susceptible patient. This reasoning is consistent with a concept of genetic heterogeneity as an explanation for familial carcinoma of the breast. This phenomenon is not unlike the current explanation for the genetics of the mucopolysaccaridoses, the lipidoses and several other major disorders of man which show genetic heterogeneity.

Although breast carcinoma is the most frequently occurring cancer in American women and has been the subject of extensive epidemiologic investigation, little attention has been devoted to use of risk-factor information in its control. Six of our 52 breast-cancer-prone families have at least one woman who has manifested breast cancer at age 30 or earlier. One such family had two women with breast cancer before age 30, and at least ten others affected by age 50. Transmission of this lesion was consistent with autosomal-dominant mode of inheritance. Ages of onset indicated a notably early peak, in contrast with the expected pre- and post-menopausal peaks in findings of the New York State Tumor Resistry and others. Genetic and epidemiologic information should be utilized to control breast cancer in certain families.