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

NCT07447544 | Active Not Recruiting

• 2 other identifiers: OI-AKRA-CNS-20250120-315/2025-2711-3
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Central Nervous System Metastases

Keywords

early-stage breast cancer; molecular biomarkers

Outcome Measures

Primary Outcomes (1)

• Differential Gene Expression in Primary Tumor Tissue Associated With CNS Metastases

  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.

  Up to 36 months after baseline

Secondary Outcomes (1)

• Association Between Baseline Serum Chemokine Concentrations and CNS Metastases

  Up to 36 months after baseline

Other Outcomes (1)

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

  Up to 36 months after baseline

Study Arms (2)

CNS Metastases Group

EXPERIMENTAL

Female patients with early-stage breast cancer who developed central nervous system (CNS) metastases during follow-up. Participants undergo molecular biomarker assessment consisting of primary tumor mRNA gene expression profiling using next-generation sequencing (NGS) and measurement of baseline serum chemokine concentrations (CX3CL1, CXCL13, CXCL8 \[IL-8\]) using ELISA.

Diagnostic Test: Primary Tumor mRNA Expression Profiling (NGS); Diagnostic Test: Serum Chemokine Quantification (ELISA)

Control Group (No CNS Metastases)

ACTIVE COMPARATOR

Matched female patients with early-stage breast cancer who did not develop CNS metastases during follow-up. Participants undergo molecular biomarker assessment consisting of primary tumor mRNA gene expression profiling using next-generation sequencing (NGS) and measurement of baseline serum chemokine concentrations (CX3CL1, CXCL13, CXCL8 \[IL-8\]) using ELISA.

Diagnostic Test: Primary Tumor mRNA Expression Profiling (NGS); Diagnostic Test: Serum Chemokine Quantification (ELISA)

Interventions

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.

CNS Metastases Group; Control Group (No CNS Metastases)

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.

CNS Metastases Group; Control Group (No CNS Metastases)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Oncology Ljubljana: lead

Study Sites (1)

Institute of Oncology Ljubljana

Ljubljana, 1000, Slovenia

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be assigned to two parallel groups based on clinical outcome during follow-up (CNS metastases vs. no CNS metastases). Both groups undergo biomarker assessment (primary tumor gene expression profiling and ctDNA ddPCR analysis).

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: March 3, 2026
• Study Start: July 7, 2025
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

SL (1)