Adjuvant Radiotherapy on Circulating Cells in Breast Cancer Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: blood samples collection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GROUP I/GROUP I bis<br>20 breast cancer patients who performed radiotherapy treatment | Other: blood samples collection<br>* 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.<br>|
| GROUP II<br>maximum 10 patients who performed radiotherapy and chemotherapy and/or immunotherapy and/or neo-adjuvant hormone therapy or/and adjuvant immunotherapy/hormone therapy. | Other: blood samples collection<br>* 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.<br>|
| CONTROLS GROUP<br>healthy women with +/- 5 years compared to breast cancer patients age | Other: blood samples collection<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, circulating bone marrow-derived cells, circulating immune cells, radiotherapy, conservative treatment, disease control