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NCT Number: NCT07447544

Predictive Factors for CNS Metastases in Early Breast Cancer Using Liquid Biopsy (AKRA CŽS)

Breast cancer is the most common cancer in women. Although most patients are diagnosed at an early stage and treated with curative intent, some later develop metastases to the central nervous system (CNS), which are associated with poor prognosis and high morbidity. Currently, there are no validated biomarkers that reliably predict which patients with early-stage breast cancer are at increased risk for CNS metastases.

This study aims to identify molecular predictors of CNS metastases in early breast cancer. Gene expression profiles (mRNA) from archived primary tumor tissue will be analyzed using next-generation sequencing (NGS). In addition, serum concentrations of chemokines CX3CL1, CXCL13, and CXCL8 (IL-8), measured at the time of diagnosis using ELISA, will be evaluated for their association with subsequent CNS metastases.

The results may improve risk stratification and support earlier identification of patients at increased risk for CNS spread.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Central Nervous System Metastases Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Institute of Oncology Ljubljana

Ljubljana, 1000, Slovenia

About this study

Breast cancer is frequently diagnosed at an early stage. Despite appropriate curative treatment, a subset of patients develops distant metastases during follow-up. Metastases to the central nervous system (CNS) represent a serious clinical complication due to their significant impact on morbidity and mortality. At present, no validated blood-based biomarkers are available to reliably predict CNS dissemination in patients with early-stage breast cancer.

The primary objective of this study is to identify genes that are differentially expressed in archived primary breast tumor tissue of patients who subsequently developed CNS metastases compared with matched controls who did not develop CNS metastases. Gene expression will be assessed using next-generation sequencing (NGS) of cDNA derived from mRNA.

The secondary objective is to evaluate whether baseline serum concentrations of chemokines CX3CL1, CXCL13, and CXCL8 (IL-8), measured using enzyme-linked immunosorbent assay (ELISA), are associated with the later development of CNS metastases.

The study includes two clinically comparable groups of patients with early-stage breast cancer:

patients who developed CNS metastases during follow-up, and

matched control patients without CNS metastases.

Statistical analyses will include descriptive statistics, univariate and multivariate logistic regression models, and receiver operating characteristic (ROC) curve analysis to evaluate predictive performance of the investigated biomarkers.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Female patients aged 18 years or older.
  • Diagnosis of early-stage breast cancer.
  • Availability of archived primary tumor tissue suitable for mRNA analysis.
  • Availability of serum sample suitable for chemokine analysis.
  • Patients included in the AKRA cohort with documented follow-up data.
  • Patients with confirmed CNS metastases during follow-up (CNS metastases group) or matched controls without CNS metastases (control group).

Exclusion criteria

  • Male breast cancer patients.
  • Lack of sufficient primary tumor tissue for mRNA analysis.
  • Lack of available serum sample for chemokine analysis.
  • Incomplete clinical follow-up data preventing classification of CNS metastasis status.

Treatment and study plan

Primary Tumor mRNA Expression Profiling (NGS)

Diagnostic Test

Gene expression profiling of mRNA derived from archived primary breast tumor tissue using next-generation sequencing (NGS) to identify genes differentially expressed between patients who developed CNS metastases and matched controls.

Serum Chemokine Quantification (ELISA)

Diagnostic Test

Measurement of serum concentrations of chemokines CX3CL1, CXCL13, and CXCL8 (IL-8) collected at diagnosis using enzyme-linked immunosorbent assay (ELISA) to evaluate their association with subsequent CNS metastases.

Primary outcomes

  1. Differential Gene Expression in Primary Tumor Tissue Associated With CNS Metastases

    Time frame: Up to 36 months after baseline

    Identification of genes differentially expressed in primary breast tumor tissue between patients who developed CNS metastases and matched controls without CNS metastases, assessed by mRNA expression profiling using NGS.

Secondary outcomes

  1. Association Between Baseline Serum Chemokine Concentrations and CNS Metastases

    Time frame: Up to 36 months after baseline

    Assessment of serum concentrations of CX3CL1, CXCL13, and CXCL8 (IL-8) measured at diagnosis using ELISA and their association with subsequent development of CNS metastases during follow-up.

Other outcomes

  1. Predictive Performance of Combined Molecular Biomarker Model for CNS Metastases (ROC Analysis)

    Time frame: Up to 36 months after baseline

    Evaluation of predictive accuracy of combined molecular biomarkers (mRNA expression profiles and serum chemokine concentrations) together with clinical-pathological variables using ROC curve analysis.

Sponsors and collaborators

Lead sponsor

Institute of Oncology Ljubljana

Other

Registry information

Official study title

Predictive Factors in Primary Tumor and Liquid Biopsy for the Spread of Early Breast Cancer to the Central Nervous System

Acronym: AKRA CŽS

Important dates

Study start
2025
Primary completion
2025
Study completion
2027
First posted
Mar 3, 2026
Registry last updated
Mar 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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