Wound response after intraoperative radiotherapy

Activation of the inflammatory wound response after breast surgery has been proposed as one of the mechanisms that could stimulate breast cancer (BC) recurrence formation. This hypothesis well fits with the notion that tumors behave as “wounds that do not heal” and raised the idea that targeting the inflammatory wound response immediately after surgery could also impact on the formation of recurrences. Therefore, a clearer picture of the pathways activated by the inflammatory wound response in residual BC cells and in breast microenvironment is of primary relevance in order to identify new possible lines of therapeutic intervention. The introduction of intraoperative radiotherapy (IORT) in the clinical management of BC patients has not only allowed for treatment improvement of selected patients, but has also offered the unique opportunity to study the immediate effect of radiotherapy (RT) on human tissues, in vivo. One of the key unanswered questions regarding the irradiation of peri-tumoral breast tissue is whether RT could have other effects than mere cancer cell killing and how these additional effects impact on the wound response of BC patients. Here, we review the last evidences connecting breast surgery to the formation of BC recurrences and the effects of breast irradiation with IORT to the modification of the wound response. Moreover, we highlight the possibility to employ new specific peri-operative intervention that, by targeting the wound response in the appropriate window of time, administered alone or in association with IORT, may prevent BC recurrence formation.