Relationship of cellular immunity, cytokines and CRP with clinical course in breast cancer patients with endocrine-dependent distant metastases treated with immunotherapy

We have reported important benefits and survival with an immunotherapy schedule in patients with endocrine-dependent breast cancer and distant metastases. Here clinical outcome is updated and its correlation with new immunological data is shown. In 32 evaluated breast cancer patients with endocrine-dependent distant metastases treated with a new immunotherapy schedule (cyclic administration of b-interferon and interleukin-2), cellular immunity, cytokines and CRP were related to the clinical course. Estimated and true 5-10 year overall survival rates from first line antiestrogen and distant metastases were higher than previously reported in a similar population. Interleukin-2 administration was followed by a significant increase in total lymphocytes, CD4+, CD8+, CD16+56+ (NK) cells, IL-6, IL-12, and CRP (from P < 0.04 to P < 0.000) but no change in IL-10 and TGFb1 during clinical benefit. During progressive disease no change was observed in the former parameters, concomitant with a significant increase in IL-10 (P = 0.020) and a significant decrease in TGFb1 (P = 0.023). These findings confirm that cellular immunity is significantly stimulated by IL-2 only during clinical benefit. Furthermore, these results demonstrate that different changes of proinflammatory cytokines, CRP and inhibiting factors are consistent with associated clinical benefit or with disease progression, respectively.