The Composition of Surgical Wound Fluids from Breast Cancer Patients is Affected by Intraoperative Radiotherapy Treatment and Depends on the Molecular Subtype of Breast Cancer

Abstract

Invasive oncological procedures affect the remaining tumor cells by increasing their survival, proliferation, and migration through the induction of wound healing response. The phenomena of local relapse after breast-conserving surgery (BCS) has resulted in a series of research and clinical trials with the aim of assessing whether localized intraoperative radiotherapy (IORT), may be beneficial in inhibiting local recurrences. Therefore, it is essential to assess the impact of intraoperative radiotherapy in modulating the immunological response and wound healing process. Thus, we decided to perform a quantitative analysis of the composition of surgical wound fluids (SWF) in two groups of breast cancer (BC) patients: those treated with BCS followed by IORT, and those who underwent BCS alone. We found that several cytokines, which are believed to have anti-tumor properties, were highly expressed in the luminal A breast cancer subtype in the IORT treatment group. Interestingly, we also found significant differences between IORT patients with tumors of different molecular subtypes. Based on these findings, we hypothesized that IORT treatment might be beneficial in changing the tumor bed microenvironment, making it less favorable for tumor recurrence due to decreased concentration of tumor-facilitating cytokines, especially in the luminal A subtype of BC.

Wound Fluid from Breast Cancer Patients Undergoing Intraoperative Radiotherapy Exhibits an Altered Cytokine Profile and Impairs Mesenchymal Stromal Cell Function

“…Confirming previous observations that IORT has an impact on cytokine levels within the WF [ 22 , 24 ], we observed that especially cytokines associated with wound healing and inflammation were modified by IORT. Oncostatin-M (OSM) was reduced in IORT-WF, whereas the levels of leptin and IL-1β were increased.…”

“…Belletti et al also observed significantly altered levels of the immune response-related cytokines IL-10 and IL-13 [ 22 ]. Elevated IL-1β levels were also reported by Kulcenty et al [ 24 ]. However, they observed that, only WF of Luminal A breast cancer patients, but not that of the Luminal B subtype [ 24 ] showed IORT-mediated increased IL-1β levels.…”

“…Further, recent studies describe the influence of IORT on the cytokine composition of surgical wound fluid (WF) [ 22 , 23 , 24 ]. Belletti et al made an essential contribution by examining the proteomic and functional properties of WF gained from wound drainages 24 h after BCS with and without IORT.…”

Surgical Wound Fluids from Patients with Breast Cancer Reveal Similarities in the Biological Response Induced by Intraoperative Radiation Therapy and the Radiation-Induced Bystander Effect—Transcriptomic Approach

“…Those authors found that SWF from patients after BCS stimulates the proliferation, invasion, and migration of breast cancer cells, but administration of IORT abrogates this effect. Previously, we have conducted the quantitative analysis of SWF composition in breast cancer (BC) patients treated with BCS only, and BCS followed by IORT, and found significant changes based not only on the applied treatment but also on the molecular subtype of BC [11]. Moreover, our group showed that the radiation-induced bystander effect (RIBE) alters the biological activity of SWF after IORT [12,13].…”

“…It is known that irradiation changes the profile of secreted cytokines. We have previously shown that composition of SWF from BCS and IORT patients differs significantly based on cytokine and growth-factor concentrations [11].…”