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

Sponsor
University of Jena (Other)
Overall Status
Recruiting
CT.gov ID
NCT04902937
Collaborator
University Hospital Erlangen (Other), Labor Prof. Pachmann (Other)
200
1
66
3

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • 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 Design

Study Type:
Observational
Anticipated Enrollment :
200 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Association of Adjuvant Radiotherapy of Non-metastatic Breast Carcinoma With Immunomodulation and Circulating Tumor Cell Phenotype in Relation to Patient Age.
Actual Study Start Date :
Jul 1, 2021
Anticipated Primary Completion Date :
Dec 31, 2026
Anticipated Study Completion Date :
Dec 31, 2026

Arms and Interventions

Arm 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

    Outcome Measures

    Primary Outcome Measures

    1. Age-dependent influence of radiotherapy on circulating epithelial tumor cell counts (CETC) and immunophenotype (PBMC). [observation period 2 years]

      Measurement of CETC count / µl blood in the course of therapy and correlation with patient age.

    2. Longitudinal quantification of CETCs as well as immunophenotype at specific time points during the course of therapy. [observation period 2 years]

      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.

    3. Comparison of immunohistochemical parameters of the primary tumor with the immunohistochemical and cytological parameters of CETC [observation period 2 years]

      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.

    Secondary Outcome Measures

    1. Recurrence-free survival (RFS) [observation period 3 years follow up]

      Recurrences as a function of time (analysis using Kaplan-Meier curves, log-rank test, and Cox regression).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Radiooncology, Jena Jena Germany 07743

    Sponsors and Collaborators

    • University of Jena
    • University Hospital Erlangen
    • Labor Prof. Pachmann

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Matthias Mäurer, Dr. med., University of Jena
    ClinicalTrials.gov Identifier:
    NCT04902937
    Other Study ID Numbers:
    • CETC 002
    First Posted:
    May 26, 2021
    Last Update Posted:
    Oct 6, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Matthias Mäurer, Dr. med., University of Jena
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 6, 2021