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| ID | Type | Description | Link |
|---|---|---|---|
| 0120-315/2025-2711-3 | Other Identifier | Clinical Research Unit, Institute of Oncology Ljubljana |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Association Between Baseline Serum Chemokine Concentrations and CNS Metastases | 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. | Up to 36 months after baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Predictive Performance of Combined Molecular Biomarker Model for CNS Metastases (ROC Analysis) | Evaluation of predictive accuracy of combined molecular biomarkers (mRNA expression profiles and serum chemokine concentrations) together with clinical-pathological variables using ROC curve analysis. | Up to 36 months after baseline |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Oncology Ljubljana | Ljubljana | 1000 | Slovenia |
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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).
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| 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. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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