Abstract
ObjectivesMesenchymal stromal cells (MSC) in bone marrow have been shown to be radioresistant, which is related to pronounced DNA repair mechanisms. Intraoperative radiotherapy (IORT) during breast-conserving surgery for early breast cancer is an innovative technique applying low energy x‑ray to the tumor bed immediately after removal of the tumor. IORT is considered to reduce the risk of local tumor recurrence by directly targeting cells of the tumor bed and altering the local microenvironment. Aim of this study was to investigate whether IORT affects the outgrowth potential of breast adipose tissue-derived MSC (bASC) as part of the tumor bed.Materials and methodsAfter surgical tumor resection, biopsies of the tumor bed were taken before (pre IORT) and after IORT (post IORT) and processed applying well-established protocols for ASC isolation and characterization.ResultsIn all, 95% of pre IORT tumor bed samples yielded persistently outgrowing bASC with typical ASC characteristics: fibroblastoid morphology, proliferation, adipogenic and osteogenic differentiation and ASC surface marker expression. However, none of the post IORT samples yielded persistent outgrowth of bASC.ConclusionsAfter breast-conserving surgery, approximately 90% of local recurrences emerge in close proximity to the initial tumor bed, potentially reflecting a significant contribution of the tumor bed to relapse. Our data show that IORT, besides the proven effect on breast cancer cells, efficiently modifies the tumor environment by having an impact on tumor bed bASC. This effect on tumor bed stromal cells might contribute to reduce the risk of tumor relapse and metastases.
Highlights
Breast cancer is the most frequent malignant tumor in women
Our results indicate that intraoperative radiotherapy (IORT) entirely abolishes the adhesion and proliferation potential of breast adipose tissue-derived MSC (bASC), suggesting radiosensitivity of bASC, at least in situ
Since IORT is performed with 20 Gy prescribed to the applicator surface in a single session, supporting data that doses higher than 10 Gy radiosensitize Mesenchymal stromal cells (MSC) [9, 14]
Summary
Breast cancer is the most frequent malignant tumor in women. Chemotherapeutic and receptortargeted therapy, local radiotherapy completes the mainstays of treatment. While postoperative whole breast radiotherapy remains standard in patients undergoing breastconserving surgery, intraoperative radiotherapy (IORT) is increasingly implemented in clinical routine. This riskadapted concept uses low energy x-rays applied during surgery directly after excision of the tumor [1]. The idea of using local radiotherapy in general is to eliminate potentially remaining tumor cells in the tumor bed after surgery, considered as a major source for relapse [2]. With irradiation taking place in the wound cavity directly after having removed the tumor, the risk of local or temporal miss is hypothetically nonexistent
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