Intraoperative Radiotherapy of Breast Cancer and Its Biological Effects

Conservative breast cancer surgery followed by radiation therapy is the standard treatment for this type of cancer. Numerous studies demonstrate that 90% of local recurrences after traditional surgery occur in the same quadrant as the primary cancer. The published data suggest that the wound healing process after surgery alters the area surrounding the original tumor and the modified microenvironment is more favorable for the tumor to recur. The majority of metastases within scar initiated much research, and the consequences of these studies led to clinical trials aimed at assessing whether localized radiotherapy, such as intraoperative radiotherapy (IORT), would be more effective in inhibiting formation of local recurrence than the standard postoperative whole breast radiotherapy. IORT involves irradiation of diseased tissue directly during surgery. The rationale for this approach is the fact that the increase in the radiation dose increases local tumor control, which is the primary goal of radiation therapy. The biological basis of this process are still not thoroughly understood. Gaining new knowledge about the recurrence formation at the molecular level could serve as a starting point for further analysis and to create an opportunity to identify new targets of therapy, and possibly new therapeutic agents.

[1]  D. Murawa,et al.  Effect of surgical wound fluids after intraoperative electron radiotherapy on the cancer stem cell phenotype in a panel of human breast cancer cell lines , 2016, Oncology letters.

[2]  G. Russo,et al.  High-dose Ionizing Radiation Regulates Gene Expression Changes in the MCF7 Breast Cancer Cell Line. , 2015, Anticancer research.

[3]  H. Forrester,et al.  Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects. , 2015, Cancer letters.

[4]  P. Lara,et al.  Direct and bystander radiation effects: a biophysical model and clinical perspectives. , 2015, Cancer letters.

[5]  F. Vicini,et al.  Intraoperative Radiation Therapy: A Critical Analysis of the ELIOT and TARGIT Trials. Part 2—TARGIT , 2014, Annals of Surgical Oncology.

[6]  A. Vecchione,et al.  Surgery-induced wound response promotes stem-like and tumor-initiating features of breast cancer cells, via STAT3 signaling , 2014, Oncotarget.

[7]  A. Vecchione,et al.  p70S6 kinase mediates breast cancer cell survival in response to surgical wound fluid stimulation , 2014, Molecular oncology.

[8]  E. Ozanne,et al.  Application of a decision analytic framework for adoption of clinical trial results: are the data regarding TARGIT-A IORT ready for prime time? , 2014, Breast Cancer Research and Treatment.

[9]  L. Esserman,et al.  Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial , 2014, The Lancet.

[10]  C. Yee,et al.  The Effect of Radiation on the Immune Response to Cancers , 2014, International journal of molecular sciences.

[11]  R. Bristow,et al.  Inhibition of breast cancer local relapse by targeting p70S6 kinase activity. , 2013, Journal of molecular cell biology.

[12]  A. Luini,et al.  Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. , 2013, The Lancet. Oncology.

[13]  Ming Li,et al.  The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. , 2013, Neoplasia.

[14]  Tiejun Wang,et al.  Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice , 2013, Cancer Cell International.

[15]  P. Kaur,et al.  Radiation-induced effects and the immune system in cancer , 2012, Front. Oncol..

[16]  Mithat Gönen,et al.  The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors. , 2011, The Journal of clinical investigation.

[17]  T. Herman,et al.  Radiation-triggered Tumor Necrosis Factor (TNF) α-NFκB Cross-signaling Favors Survival Advantage in Human Neuroblastoma Cells* , 2011, The Journal of Biological Chemistry.

[18]  T. Fenton,et al.  Functions and regulation of the 70kDa ribosomal S6 kinases. , 2011, The international journal of biochemistry & cell biology.

[19]  Jae-Seon Lee,et al.  Time-dependently expressed markers and the characterization for premature senescence induced by ionizing radiation in MCF7. , 2010, Oncology reports.

[20]  L. Esserman,et al.  Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial , 2010, The Lancet.

[21]  M. Hung,et al.  The Expression Patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by Immunohistochemical Analysis in Breast Cancer Cell Lines , 2010, Breast cancer : basic and clinical research.

[22]  Jason R. Pirone,et al.  Activation of Host Wound Responses in Breast Cancer Microenvironment , 2009, Clinical Cancer Research.

[23]  David A Hess,et al.  High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability , 2009, Journal of cellular and molecular medicine.

[24]  L. Elmore,et al.  Accelerated senescence: an emerging role in tumor cell response to chemotherapy and radiation. , 2008, Biochemical pharmacology.

[25]  F. Lovat,et al.  Targeted Intraoperative Radiotherapy Impairs the Stimulation of Breast Cancer Cell Proliferation and Invasion Caused by Surgical Wounding , 2008, Clinical Cancer Research.

[26]  F. Sedlmayer,et al.  The Salzburg concept of intraoperative radiotherapy for breast cancer: Results and considerations , 2006, International journal of cancer.

[27]  J. Little,et al.  Cellular mechanisms for low-dose ionizing radiation-induced perturbation of the breast tissue microenvironment. , 2005, Cancer research.

[28]  N. Thompson,et al.  MammoSite Radiation Therapy System. , 2005, Clinical journal of oncology nursing.

[29]  M. Baum,et al.  TARGeted Intraoperative radiotherapy (TARGIT): an innovative approach to partial-breast irradiation. , 2005, Seminars in radiation oncology.

[30]  R. Simmons,et al.  Locally recurrent breast cancer after conservation therapy. , 2005, American journal of surgery.

[31]  C. Mothersill,et al.  Radiation-induced bystander effects — implications for cancer , 2004, Nature Reviews Cancer.

[32]  V. Steil,et al.  A Novel Mobile Device for Intraoperative Radiotherapy (IORT) , 2003, Oncology Research and Treatment.

[33]  M. Campiglio,et al.  Role of HER2 in wound-induced breast carcinoma proliferation , 2003, The Lancet.

[34]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  A. Luini,et al.  Intraoperative Radiation Therapy for Breast Cancer: Technical Notes , 2003, The breast journal.

[36]  F. Vicini,et al.  MammoSite radiation therapy system. , 2003, Breast.

[37]  E Marubini,et al.  Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[38]  Michael L. Bittner,et al.  Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  M Ciocca,et al.  A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated. , 2001, European journal of cancer.

[40]  J. Bromberg Signal transducers and activators of transcription as regulators of growth, apoptosis and breast development , 2000, Breast Cancer Research.

[41]  D T Goodhead,et al.  Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. , 1994, International journal of radiation biology.

[42]  W. Haseltine,et al.  Sites and structure of gamma radiation-induced DNA strand breaks. , 1982, The Journal of biological chemistry.