Peri-Operative Suppression of Immune-Regulatory Blood Cells Predicts Wound Complications in Breast Cancer Patients.

Abstract

IntroductionWe have previously demonstrated an association between post-operative wound complications and systemic breast cancer recurrence (p<0.0001), Murthy et al (2007) Br J Cancer 97, 1211-7. The aim of this study was to examine the potential role of the immune system in establishing this association, and therefore whether immune factors might be used to predict either wound complications or cancer recurrences.MethodsPatients with primary operable breast cancer were prospectively recruited to the study. Serial blood investigations were performed pre-operatively, peri-operatively and post-operatively. Absolute numbers of various lymphocyte cell populations were measured using multi-colour flow-cytometry including CD45+lymphocytes, CD19+ B lymphocytes, CD3+ T lymphocytes, CD4+ helper T cells, CD8+ cytotoxic T cells and CD56+ NK cells. We also measured the levels of the NK cytotoxicity receptors NKp30 and NKp46 on the NK cell population.ResultsOne hundred and nine patients were recruited to the study and there was a wound complication rate of 13.4%. Absolute numbers of CD3+ T lymphocytes, CD4+ helper T cells, CD8+ cytotoxic T cells and CD56+ NK cells were significantly lower 4 hours post-operatively compared to pre-operative levels (p<0.05), although levels had typically recovered after 24 hours. However, NKp30 expression remained significantly reduced at 24 hours (p<0.05). Mastectomy patients had a significantly greater fall in T lymphocyte numbers than those having breast conserving surgery (p<0.05). Patients who went on to develop wound complications post-operatively had a significantly greater fall in their CD4+ helper T cells at 4 hours post-operatively, than those patients who did not go on to develop wound complications (p<0.05).ConclusionsBreast cancer surgery results in severe disruption to the immune system, with dramatic changes in levels of immune regulatory blood cells populations. Changes are predominantly immuno-suppressive. The greater the immune disruption as a result of surgery, the more likely the patient is to develop a wound complication. We believe that this peri-operative immuno-suppression may also provide a window of opportunity for the successful dissemination of tumour cells post-operatively thereby increasing the risk of future metastases; we are maintaining follow up on this patient cohort in order to test correlations between peri-operative immuno-suppression and systemic recurrences. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4132.