Human lymphocyte blastogenesis responses to mouse mammary tumor virus

Cellular immune responses to antigens associated with mouse mammary tumor virus were evaluated in 101 human female subjects with the use of the lymphocyte blastogenesis assay. Positive responses (stimulation index, >3.0) were seen in 18 of 61 (30%) breast cancer female patients and 2 of 21 (9%) normal female controls. Not only did breast cancer patients respond more frequently but also their stimulation indices were substantially higher than those of the control group. The differences between the two populations had a high degree of statistical significance (P<0.002, t-test; P<0.017, Mann-Whitney U test). Positive responses were not explainable as nonspecific cross-reactivity because simultaneous tests with Rauscher murine leukemia virus or normal mouse tissue antigens failed to reveal correlating lymphocyte stimulation. Ordinary contact with patients did not appear to influence the frequency of positive cellular responses on the part of normal women. However, female laboratory workers, presumably in contact with mice or mouse viruses, showed frequent reactivity and thus were not considered normal controls. Frequently, reactivity (3/10 subjects) was also seen in a small panel of women with a history of benign breast disease. The study revealed a highly significant association between human breast cancer and in vitro cellular responses to mouse mammary tumor virus, as documented by the lymphocyte blastogenesis assay. Because selected normal populations also showed reactivity, further studies with this technique should be conducted with careful scrutiny of possible environmental, genetic, and clinical correlations among the tested subjects.