Immunocompetence, immunosuppression, and human breast cancer. I. An analysis of their relationship by known parameters of cell-mediated immunity in well-defined clinical stages of disease.
General immune competence was examined 255 breast cancer patients, including 104 operable, 44 locally advanced/inoperable, and 44 with demonstrable metastatic dissemination, all at the time of diagnosis, as well as 63 disease-free long survivors; this was compared with that of 100 normal controls. The parameters employed were PPD and DNCB skin testing, lymphocyte response to PHA mitogen, E-rosette formation, and lymphocyte number. Significant patients, with only 31% showing optimal and 25% showing minimal levels of immune function, as compared with 70% optimal and 2% minimal function in controls. Immune competence was not affected by metastatic involvement of regional lymph nodes. In patients with early, occult metastatic dissemination (as determined in retrospect), the degree of immune competence was found to be identical to that of patients who did not develop disease dissemination. Remarkably, this early phase of tumor spread is not accompanied by immune impairment, such as is evident in clinically demonstrable metastatic disease and, to a lesser degree, in advanced local and regional disease. Since tumor dissemination preceded impairment of general immunocompetence, it emerges as the cause rather than the result of immunosuppression. Long disease-free survivors, who had postoperative irradiation 5-12 years previously, were shown to have a notably low level of immune competence. Lymphocyte response to PHA stimulation was found to be impaired in the earlier stages of disease, while skin DHR was still well maintained; in advanced disease both parameters tend to correlate as total immunologic impairment ensues. The sequence of immunologic events leading up to immunosuppression with disease progress is discussed.