Boomsma et al. [1] determined endocrine and immune responses to surgery in 27 patients with breast cancer and concluded that surgical procedure produced substantial immunomodulation. The study was well designed and conducted, while we have some concern about its data interpretation.
In this study, cytokines produced by peripheral blood mononuclear cells (PBMC) upon mitogenic or inflammatory stimulation rather than levels of T helper (Th)1/Th2 cytokines in the sera were detected to identify the surgery-related changes of serum cytokines [1]. As a result, the authors revealed a pro-inflammatory status indirectly induced by breast cancer surgery, whereas the direct surgery-related immunomodulation was not shown. In this regard, the results would be more convincing if the authors could detect the serum levels of Th1 and Th2 cytokines. Th1 cells predominantly secrete interferon (IFN)-g and tumor necrosis factor (TNF)-a while Th2 cells predominantly secrete interleukin (IL)-4, IL-5, . Although IL-12 is crucial to induce Th1 cells and polarize a Th1 response, it is not a Th1 cytokine, since it is primarily produced by antigen presenting cells such as macrophages and dendritic cells [3][4][5][6][7]. Similarly, IL-6 is a classic proinflammatory cytokine but not a typical Th2 cytokine [7]. We are also eager to know if there is any correlation between perioperational cytokine/cortisol alteration and breast cancer staging. If so, surgery-induced immunomodulation might also be confounded by cancer stages because more tumor cells may shed into circulation in cases with more advanced cancer. It is also the case if the authors concluded that no cortisol response occurred after breast cancer surgery, because breast cancer surgery is a minor type of surgery. Another potential confounding factor is peri-operational infection, especially with regard to unexpected increase in Th1 cytokines (IL-2 and TNF-a) 5 days after surgery, contrary to former findings [8]. Therefore, any subject with peri-surgical fever indicating infections should be excluded from the study.
In summary, surgical procedure produces of breast cancer, although conventionally considered minor, may induce substantial immunomodulation. Further studies are needed to either utilize or prevent this immunoregulatory effect.