Breast Cancer, Central Nervous System Metastases
Conditions
Keywords
early-stage breast cancer, molecular biomarkers
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTPrimary Tumor mRNA Expression Profiling (NGS)
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.
DIAGNOSTIC_TESTSerum Chemokine Quantification (ELISA)
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.
Sponsors
Institute of Oncology Ljubljana
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
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).
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differential Gene Expression in Primary Tumor Tissue Associated With CNS Metastases | 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
| Measure | Time frame | Description |
|---|---|---|
| Association Between Baseline Serum Chemokine Concentrations and CNS Metastases | 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. |
Countries
Slovenia
Outcome results
None listed