Association of Adjuvant Radiotherapy of Non-metastatic Breast Carcinoma With Immunomodulation and Circulating Tumor Cell Phenotype in Relation to Patient Age. (CETC)

In a prospective study, the influence of adjuvant radiotherapy in patients with non-metastatic breast carcinoma on the epithelial tumor cells (CETCs) circulating in the blood and their immunohistochemical characteristics depending on age will be investigated. In addition to a histopathological assignment of the CETCs as cells of the primary tumor, major trigger points of the immune system will be exploratively analyzed.

For this purpose, blood samples are taken from the patients at different time points after tumor resection and during adjuvant radiotherapy. In addition to the detection, isolation and genetic characterization of the CETCs, the determination of immunological biomarkers by immunophenotyping, among other methods, is planned. Furthermore, analyses of tissue from the primary tumor with respect to immunohistochemical features as well as tumor-infiltrating lymphocytes (TILs) are planned. The results will be classified and correlated especially with regard to patient age.

As there are insufficient data available for breast carcinoma regarding radiotherapeutic effects on the immune system depending on patient age, it is of great interest to better understand these molecular biological basics in order to identify potential prognostic biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Tumor Cell, Circulating
• Intervention / Treatment: Radiation: Adjuvant radiotherapy; Drug: neoadjuvant and adjuvant chemotherapy

Detailed Description

The primary aim of this prospective-explorative phase 0 study is to investigate the influence of adjuvant radiotherapy in patients with non-metastatic breast cancer on the circulating epithelial tumor cells (CETCs) in the peripheral blood and their immunohistochemical characteristics in younger high risk (premenopausal) versus older low risk (postmenopausal) patients. In addition, the immunophenotype will be determined using peripheral venous blood mononuclear cells (PBMCs) at different time points during the course of therapy and correlated with the results of CETC analysis. The aim of the study is to identify prognostic and predictive biomarkers for early stage breast cancer patients. No therapeutic consequences will be derived.

For this purpose, the phenotype and molecular biological profile of CETC will be investigated and compared with the corresponding characteristics of the primary tumor in order to assign the tumor cells detected in the peripheral blood to the primary tumor. In this context, the number of tumor-infiltrating lymphocytes (TILs) will be correlated with circulating tumor cells and immunophenotype.

Another goal is the characterization of individually isolated CETC by RT-PCR. The expression of selected marker genes involved in metastatic processes will be investigated during the course of therapy and compared with that of the primary tumor to identify therapy-associated changes. The in vitro cultivation of so-called tumor spheres and their characterization as a sign of a therapy-resistant phenotype is a secondary objective of the study.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Germany
  • Jena, Germany, 07743
    • Recruiting
    • Department of Radiooncology, Jena
    • Contact: Matthias A Mäurer, MD; Phone Number: +4936419328401; Email: matthias.maeurer@med.uni-jena.de
    • Principal Investigator: Matthias Mäurer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Only female patients with non-metastatic breast carcinoma undergoing breast-conserving surgery (± neoadjuvant or adjuvant system therapy) at the Department of Gynecology and Reproductive Medicine Jena followed by adjuvant radiation therapy at the Department of Radiation Oncology and Radiotherapy Jena between June 1, 2021 and June 1, 2023 (recruitment period) will be studied.

Description

Inclusion Criteria:

• Primary diagnosis histologically confirmed invasive breast carcinoma pT1-4 pN0 or pN+ cM0
• curative-intended breast-conserving therapy (BET) ± (neo-) adj. system therapy with subsequent adjuvant radiotherapy of the breast ± lymphatic drainage system planned
• informed consent of the patient

Exclusion Criteria:

• DCIS, Inflammatory breast carcinoma
• Recurrence situation
• Presence of distant metastases
• Second malignancies < 10 years prior to diagnosis of breast carcinoma
• Prior exposure to radiotherapy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
premenopausal patients	Radiation: Adjuvant radiotherapy; Guideline-based therapy of primary non-metastatic early breast carcinoma; Other Names: breast-conserving therapy; Drug: neoadjuvant and adjuvant chemotherapy; Guideline-based therapy of primary non-metastatic early breast carcinoma
postmenopausal patients	Radiation: Adjuvant radiotherapy; Guideline-based therapy of primary non-metastatic early breast carcinoma; Other Names: breast-conserving therapy; Drug: neoadjuvant and adjuvant chemotherapy; Guideline-based therapy of primary non-metastatic early breast carcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age-dependent influence of radiotherapy on circulating epithelial tumor cell counts (CETC) and immunophenotype (PBMC).	Measurement of CETC count / µl blood in the course of therapy and correlation with patient age.	observation period 2 years
Longitudinal quantification of CETCs as well as immunophenotype at specific time points during the course of therapy.	Measurement of CETC count / µl blood in the course of therapy and correlation with the cell count of detected T and B cells / µl blood.	observation period 2 years
Comparison of immunohistochemical parameters of the primary tumor with the immunohistochemical and cytological parameters of CETC	Comparison of PD-L1 expression of primary tumor cells with CETC in percent. Comparison of hormone receptor status (estrogen, progesterone) values of primary tumor and CETC in percent.	observation period 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival (RFS)	Recurrences as a function of time (analysis using Kaplan-Meier curves, log-rank test, and Cox regression).	observation period 3 years follow up

Collaborators and Investigators

• Sponsor: University of Jena
• Collaborators: University Hospital Erlangen; Labor Prof. Pachmann

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Radiotherapy; Tumor-infiltrating lymphocytes; Circulating Tumor Cells; Immunophenotyping; Early Stage Breast cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Neoplasm Metastasis; Breast Neoplasms; Neoplastic Cells, Circulating
• Other Study ID Numbers: CETC 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No