Adjuvant Radiotherapy on Circulating Cells in Breast Cancer Patients

Breast Cancer Clinical Trial

— CCB-RT  

Official title:

Effects of Adjuvant Radiotherapy on Bone-marrow Derived and Immune Cells in Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04002570
• Other study ID #: CirculatingCellsBreast-RT
• Status: Completed
• Start date: October 25, 2015
• Est. completion date: December 30, 2020

Study information

• Verified date: April 2021
• Source: Clinica Luganese Moncucco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Radiation applied to the preserved breast during radiotherapy treatment activates numerous molecular cascades in tumor bed adjacent cells causing an inflammatory state. During this process, pre-clinical studies demonstrated CD11b + and CD11b+cKit+cells mobilization in the blood. These cells are involved in numerous processes during tumor progression/control and metastases development. The expected results in clinical setting allow us to investigate the development of innovative therapeutic and monitoring strategies. The clinical repercussions would consist in identifying new predictive and prognostic targets in breast cancer.

Description:

Every year, around one million women are newly diagnosed with breast cancer. Early screening and adjuvant treatments with curative intent such as radiotherapy, hormone therapy, chemotherapy, immunotherapy, have reduced the incidence of breast cancer specific mortality. Despite this, breast cancer remains the main cause of cancer mortality in Europe. The primary cause is due to metastases development in different organs, such as lung, liver, bones and brain. A significant decrease in mortality in breast cancer patients is likely to be achieved by preventing the formation of metastases or by implementing the efficacy of their treatment. Radiotherapy is one of the pillars of breast cancer adjuvant treatments with important survival benefits.

Mutual and dynamic communications between tumor cells and the tumor microenvironment (TME) influence the development and evolution of the tumor as well as the appearance of distant metastases. The mediators of the immune and inflammatory response that constitute TME, as well as mediators of tumor progression, are also considered "targets" of future therapeutic strategies.

Radiation applied to the preserved breast during radiotherapy treatment activates numerous molecular cascades in tumor bed adjacent cells causing an inflammatory state. During this process, pre-clinical studies demonstrated CD11b + and CD11b+cKit+cells mobilization in the blood. These cells are involved in numerous processes during tumor progression/control and metastases development. The results allow us to investigate the development of innovative therapeutic and monitoring strategies. The clinical repercussions would consist in identifying new predictive and prognostic targets in breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: December 30, 2020
• Est. primary completion date: September 15, 2020
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• breast cancer diagnosis bioptically proven with pre-operative clinical stage cT1-4, N0-1, M0;

• patients who are candidates for conservative surgery (tumorectomy / quadrantectomy +/- lymphadenectomy or sentinel lymph node) or patients already undergoing conservative surgery;

• patients who are candidates for an adjuvant mammary radiotherapy treatment +/- adjuvant or neoadjuvant chemotherapy due to a triple negative or a high ki67 value that has indicated it;

• understanding of the Italian language for the Coordinating Center, understanding of the French language for the satellite center.

Exclusion Criteria:

• previous mastectomy surgery;

• concomitant cancer diseases;

• previous chemo / radiotherapy treatments in the last three years.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Other:
• blood samples collection
blood samples collection are performed at 4 different timepoints: preop, pre rt, week 6 rt, week 12-14 (fu) for GROUP I and GROUP II; blood samples collection are performed at 3 different timepoints: pre rt, week 6 rt, week 12-14 (fu) for GROUP I bis; blood samples collection are performed just once for control GROUP.

Locations

Country	Name	City	State
Switzerland	Clinica Luganese Moncucco	Lugano	Ticino

Sponsors (4)

Lead Sponsor	Collaborator
Clinica Luganese Moncucco	Curzio Rüegg, MD, Head of Department, University of Fribourg, Swiss National Science Foundation, Tsoutsou Pelagia MD, Head of Radation Therapy Department

Country where clinical trial is conducted

Switzerland, 

References & Publications (16)

[The Helsinki Declaration of the World Medical Association (WMA). Ethical principles of medical research involving human subjects]. Pol Merkur Lekarski. 2014 May;36(215):298-301. Polish. — View Citation

Boylan AM, Rüegg C, Kim KJ, Hébert CA, Hoeffel JM, Pytela R, Sheppard D, Goldstein IM, Broaddus VC. Evidence of a role for mesothelial cell-derived interleukin 8 in the pathogenesis of asbestos-induced pleurisy in rabbits. J Clin Invest. 1992 Apr;89(4):1257-67. — View Citation

Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ; Panel Members. Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015 Aug;26(8):1533-46. doi: 10.1093/annonc/mdv221. Epub 2015 May 4. — View Citation

Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002 Dec 19-26;420(6917):860-7. Review. — View Citation

Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Med Etika Bioet. 2002 Spring-Summer;9(1-2):12-9. — View Citation

Dixon JR Jr. The International Conference on Harmonization Good Clinical Practice guideline. Qual Assur. 1998 Apr-Jun;6(2):65-74. — View Citation

Drooger JC, Hooning MJ, Seynaeve CM, Baaijens MH, Obdeijn IM, Sleijfer S, Jager A. Diagnostic and therapeutic ionizing radiation and the risk of a first and second primary breast cancer, with special attention for BRCA1 and BRCA2 mutation carriers: a critical review of the literature. Cancer Treat Rev. 2015 Feb;41(2):187-96. doi: 10.1016/j.ctrv.2014.12.002. Epub 2014 Dec 8. Review. — View Citation

Han M, Liew CT, Zhang HW, Chao S, Zheng R, Yip KT, Song ZY, Li HM, Geng XP, Zhu LX, Lin JJ, Marshall KW, Liew CC. Novel blood-based, five-gene biomarker set for the detection of colorectal cancer. Clin Cancer Res. 2008 Jan 15;14(2):455-60. doi: 10.1158/1078-0432.CCR-07-1801. Epub 2008 Jan 18. — View Citation

Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012 Mar 20;21(3):309-22. doi: 10.1016/j.ccr.2012.02.022. Review. — View Citation

Kuonen F, Secondini C, Rüegg C. Molecular pathways: emerging pathways mediating growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment. Clin Cancer Res. 2012 Oct 1;18(19):5196-202. doi: 10.1158/1078-0432.CCR-11-1758. Epub 2012 Jun 22. Review. — View Citation

Lorusso G, Rüegg C. The tumor microenvironment and its contribution to tumor evolution toward metastasis. Histochem Cell Biol. 2008 Dec;130(6):1091-103. doi: 10.1007/s00418-008-0530-8. Epub 2008 Nov 6. Review. — View Citation

Rüegg C, Pytela R, Erle DJ. Characterization of the leukocyte integrin subunit beta 7. Chest. 1993 Feb;103(2 Suppl):86S. — View Citation

Rüegg C, Yilmaz A, Bieler G, Bamat J, Chaubert P, Lejeune FJ. Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma. Nat Med. 1998 Apr;4(4):408-14. — View Citation

Rüegg CR, Chiquet-Ehrismann R, Alkan SS. Tenascin, an extracellular matrix protein, exerts immunomodulatory activities. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7437-41. — View Citation

Schlaeppi M, Rüegg C, Trân-Thang C, Chapuis G, Tevaearai H, Lahm H, Sordat B. Role of integrins and evidence for two distinct mechanisms mediating human colorectal carcinoma cell interaction with peritoneal mesothelial cells and extracellular matrix. Cell Adhes Commun. 1997 Mar;4(6):439-55. — View Citation

Sharma P, Sahni NS, Tibshirani R, Skaane P, Urdal P, Berghagen H, Jensen M, Kristiansen L, Moen C, Sharma P, Zaka A, Arnes J, Sauer T, Akslen LA, Schlichting E, Børresen-Dale AL, Lönneborg A. Early detection of breast cancer based on gene-expression patterns in peripheral blood cells. Breast Cancer Res. 2005;7(5):R634-44. Epub 2005 Jun 14. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the frequency of CD11b?cKit? cells in peripheral blood and/or gene expression in circulating CD11b? cells	validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b?cKit? cells in peripheral blood and / or gene expression in circulating CD11b? cells, evaluating their trend at different time points compared to radiotherapy treatment.	pre surgery
Primary	the frequency of CD11b?cKit? cells in peripheral blood and/or gene expression in circulating CD11b? cells	validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b?cKit? cells in peripheral blood and / or gene expression in circulating CD11b? cells, evaluating their trend at different time points compared to radiotherapy treatment.	pre radiotherapy
Primary	the frequency of CD11b?cKit? cells in peripheral blood and/or gene expression in circulating CD11b? cells	validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b?cKit? cells in peripheral blood and / or gene expression in circulating CD11b? cells, evaluating their trend at different time points compared to radiotherapy treatment.	week 6 of radiotherapy
Secondary	radiotherapy alters in a potentially predictive way the frequency of CD11b?cKit? cells in peripheral blood	validate the hypothesis that adjuvant radiotherapy alters in a potentially predictive way the frequency of CD11b?cKit? cells in peripheral blood and / or gene expression in circulating CD11b? cells.	week 12-14 (fu)