Gene Methylation for Diagnosis of Breast Lesions

February 16, 2026 updated by: Institute of Oncology Ljubljana

Diagnostic Significance of BRCA1, RASSF1A and PTEN Methylation in Breast Lesions of Uncertain Malignant Potential

Breast lesions of uncertain malignant potential represent a diagnostic challenge, as conventional histopathological assessment does not always reliably distinguish between benign and malignant changes.

The purpose of this prospective diagnostic study is to evaluate whether methylation patterns of selected breast cancer-related genes (BRCA1, RASSF1A, and PTEN) can help differentiate benign from malignant breast lesions.

Tissue samples obtained during diagnostic needle biopsy, and when applicable during surgical excision, will be analyzed for gene methylation status. The results will be compared with standard histopathological findings.

The study aims to improve diagnostic accuracy in breast lesions of uncertain malignant potential and contribute to better clinical decision-making in breast diagnostics.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Breast lesions of uncertain malignant potential (B3 category) pose a significant diagnostic challenge in clinical practice, as they carry a variable risk of malignancy and often lead to surgical excision despite a substantial proportion of benign outcomes.

Epigenetic alterations, particularly DNA methylation of tumor suppressor genes, are recognized as early events in breast carcinogenesis and may provide additional diagnostic information beyond conventional histopathology.

This prospective interventional diagnostic study investigates the diagnostic significance of methylation status of BRCA1, RASSF1A, and PTEN genes in breast lesions of uncertain malignant potential. Participants undergoing diagnostic evaluation for suspicious breast lesions will be enrolled after providing written informed consent.

Tissue samples obtained during diagnostic needle biopsy will be analyzed using molecular methods to determine gene methylation status. In cases where surgical excision is performed, methylation findings from needle biopsy specimens will be compared with those from surgical samples and correlated with final histopathological diagnosis.

The primary objective is to assess whether gene methylation patterns can distinguish benign from malignant breast lesions. Secondary objectives include evaluating concordance between needle biopsy and surgical specimens and analyzing differences in methylation profiles across histopathological lesion categories.

The study is conducted at the Institute of Oncology Ljubljana and does not influence clinical decision-making. All diagnostic and therapeutic procedures follow standard clinical practice.

Study Type

Interventional

Enrollment (Actual)

401

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Institute of Oncology Ljubljana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female patients aged 18 years or older.
  • Patients referred for diagnostic evaluation of breast lesions of uncertain malignant potential.
  • Availability of breast tissue samples obtained by diagnostic needle biopsy.
  • Written informed consent for participation in the study.

Exclusion Criteria:

  • Male patients.
  • Patients younger than 18 years.
  • Patients without breast lesions or without indication for diagnostic biopsy.
  • Inadequate or insufficient tissue material for molecular analysis.
  • Withdrawal of informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Diagnostic Molecular Analysis Arm
Diagnostic test: Gene Methylation Analysis of BRCA1, RASSF1A and PTEN
Molecular analysis of BRCA1, RASSF1A, and PTEN gene methylation performed on breast tissue samples obtained during diagnostic procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Accuracy (Sensitivity and Specificity) of BRCA1, RASSF1A and PTEN Methylation for Malignancy Detection in B3 Breast Lesions
Time Frame: Baseline (needle biopsy) to final histopathological diagnosis (up to 12 months)
Diagnostic accuracy of BRCA1, RASSF1A and PTEN gene methylation status measured in diagnostic needle biopsy tissue samples for predicting malignancy (malignant vs benign final diagnosis), using final histopathological diagnosis as the reference standard. Diagnostic performance will be reported as sensitivity and specificity (%), with additional diagnostic accuracy measures (PPV, NPV and AUC).
Baseline (needle biopsy) to final histopathological diagnosis (up to 12 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concordance of BRCA1, RASSF1A and PTEN Methylation Status Between Needle Biopsy and Surgical Specimens
Time Frame: Up to 12 months after needle biopsy
Agreement of BRCA1, RASSF1A and PTEN methylation status between diagnostic needle biopsy tissue samples and matched surgical excision specimens. Concordance will be assessed using percentage agreement (%) and Cohen's kappa coefficient (κ).
Up to 12 months after needle biopsy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Oncology Ljubljana

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2024

Primary Completion (Actual)

December 31, 2025

Study Completion (Actual)

January 9, 2026

Study Registration Dates

First Submitted

February 4, 2026

First Submitted That Met QC Criteria

February 16, 2026

First Posted (Actual)

February 24, 2026

Study Record Updates

Last Update Posted (Actual)

February 24, 2026

Last Update Submitted That Met QC Criteria

February 16, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • OI-BRCA-METH-2024
  • ERIDNPVO-0048/2024 (Other Identifier: Clinical Research Unit, Institute of Oncology Ljubljana)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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