Investigation of immunoregulatory mechanisms relating to poor surgical wound healing and breast cancer recurrence

Excerpt

The factors leading to breast cancer recurrence are incompletely understood. We recently carried out a retrospective study of treatment and outcome for 1,065 breast cancer patients for which we examined factors correlating with cancer recurrence. We found that infection of surgical wounds after surgery for primary disease positively correlated with cancer recurrence [1]. Patients with wound complications were almost threefold more likely to have systemic recurrences than those without over the follow-up period (P < 0.0001). The aim of our current 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. This may be as a result of the tumour itself suppressing the activity of immune regulatory cells including dendritic cells, T cells and NK cells via increased levels of some critical cytokines (for example, vascular endothelial growth factor, IL-10, IL-6). Secondly, factors released at sites of wound complications may have direct influences on the remaining occult tumour cells, thereby increasing the likelihood of metastases. This model is supported by observations that cytokines released at sites of infection as part of inflammatory/immune responses are capable of enhancing growth and survival of tumour cells [2]. Also there is evidence that bacterial components may stimulate metastatic growth, most probably via cytokine mediators [3]. …