Immunobiology of operable breast cancer: an assessment of biologic risk by immunoparameters.

The concept of whether immune function was related to risk of recurrence was examined in patients with operable breast cancer in whom careful clinical and pathologic staging had been performed. Patients were classified according to the risk of recurrence. The "low risk" group included patients with minimal breast cancer, noninfiltrating cancer, or infiltrating cancer less than 1 cm with negative nodes. The "high ridk" group included patients with lesions greater than 1 cm or who had greater than or equal to 4 nodal metastases or who had macrometastases at Level II or III (apex). In the "intermediate risk" group were patients with infiltrating cancer less than 1 cm or with less than 4 nodal metastases at I only. Immune reactivity was assessed by skin tests, by measurement of absolute lymphocyte count, T and B cells, lymphocyte stimulation by mitogens and a battery of common antigens, serum immunoglobulins and complement levels. There were 134 patients with operable breast cancer and 63 patients with benign breast lesions. The breast cancer patients showed minimal or no impairment of DNCB skin test. Only patients with nodal metastases showed a slight but not significant impairment of DNCB responses (80% were DNCB positive compared to 90% in the controls.) The lymphocyte responses to mitogens were normal in the breast cancer patients, but there was a significant depression of lymphocyte responses to certain recall antigens such as Candida albicans and E coli. The absolute lymphocyte count and the T cell counts were normal, but B cells bearing complement receptors were decreased and B cells bearing sufface immunoglobulins were increased in the breast cancer patients. Analysis of immune function according to the pathologic stage of disease "risk of recurrence" categories showed no correlation with skin tests or lymphocyte levels. A striking and paradoxical finding was the demonstration that patients with "low risk" cancer overall had markedly lower responses to the battery of stimulating mitogens and antigens than found in patients with "high risk" or "intermediate risk" disease. Only the lymphocyte responses to PHA showed a significant linear correlation with increasing pathologic stage or "risk of recurrence." Current evidence from this study suggests that PHA response is markedly influenced by the primary tumor burdenand thus indirectly reflects the risk of recurrence.