Clinical trial NCT04902937: Association of Adjuvant Radiotherapy of Non-metastatic Breast Carcinoma With Immunomodulation and Circulating Tumor Cell Phenotype in Relation to Patient Age.
Official title: Association of Adjuvant Radiotherapy of Non-metastatic Breast Carcinoma With Immunomodulation and Circulating Tumor Cell Phenotype in Relation to Patient Age.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tumor Cell, Circulating
Keywords: Early Stage Breast cancer
Circulating Tumor Cells
Tumor-infiltrating lymphocytes
Radiotherapy
Immunophenotyping
Lead sponsor: University of Jena
Sponsor class: OTHER
Collaborators: name: University Hospital Erlangen
name: Labor Prof. Pachmann
First posted: 2021-05-26
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Age-dependent influence of radiotherapy on circulating epithelial tumor cell counts (CETC) and immunophenotype (PBMC).
timeFrame: observation period 2 years
measure: Longitudinal quantification of CETCs as well as immunophenotype at specific time points during the course of therapy.
timeFrame: observation period 2 years
measure: Comparison of immunohistochemical parameters of the primary tumor with the immunohistochemical and cytological parameters of CETC
timeFrame: observation period 2 years
Secondary outcomes:
measure: Recurrence-free survival (RFS)
timeFrame: observation period 3 years follow up
Other outcomes:
Locations:
city: Jena
country: Germany
facility: Department of Radiooncology, Jena
Study officials:
References: