Investigation of immuno-regulatory mechanisms relating to poor surgical wound healing and breast cancer recurrence.

Abstract

#5045 Background: The factors leading to breast cancer recurrence are incompletely understood. We carried out a retrospective study of outcome for 1065 breast cancer patients for which we examined factors correlating with cancer recurrence. We found that infection of wounds after surgery for primary disease positively correlated with cancer recurrence (Murthy et al, BJC 2007). Patients with wound complications were 3 fold more likely to have systemic recurrences than those without (p<0.0001). The aim of our study is to determine mechanisms responsible for this correlation. Our approach is based on two possible theories. First, patients may have an underlying immune dysfunction that predisposes them to developing both wound complications and also recurrence. Secondly, factors released at sites of wound complications may have direct influences on the remaining occult tumour cells, thereby increasing the likelihood of metastases.
 Methods: Patients with primary operable breast cancer were recruited prospectively. Blood was collected from patients pre-operatively, 4 and 16h post-operatively and again at 2 weeks, 3 and 6 months post-operatively. A variety of investigations were carried out on each sample to establish the immune status of the patient at that time point, and to identify potential mediators of cross talk between the immune system, the wound and any occult tumour cells. These investigations include: a) Full blood count; b) Immune cell phenotyping (absolute numbers/frequency of B, T lymphocytes and Natural Killer (NK) cell sub-types using multi-colour flow-cytometry); c) Cytokine profiling (using fluid phase cytometric multiplex immunoassays for 27 critical cytokines). Patients were followed up post-operatively for wound complications.
 Results:
 In our cohort of 57 patients, those who underwent a mastectomy were four times more likely to develop a post-operative wound infection than those who had breast conserving surgery (p=0.022). There was no significant difference in pre-operative absolute numbers of B and T lymphocytes or NK cells between the two groups. The percentage drop in absolute numbers of NK cells at 4 hours post-operatively was greater in the mastectomy group than in patients having breast conserving surgery (p=0.008). Mastectomy patients also dropped their CD45 counts by a significantly greater percentage (p=0.024). No significant difference was noted in the CD3, CD4, CD8 and CD19 counts between the two groups. Patients who developed wound infections showed peaks in levels of either Interleukin 5 or Interleukin 6.
 Conclusion
 Disruption of immune mechanisms as a result of increased surgical stresses in mastectomy patients contributes to a higher rate of wound complications. This may also provide a window of opportunity for the dissemination of tumour cells with their latent potential for reactivation and the development of metastases. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5045.