Diagnostic significance of silencing genes associated with breast cancer in lesions of uncertain malignant potential

The aim of the study is to determine the importance of epigenetic silencing of genes associated with breast cancer in distinguishing benign from malignant lesions and to determine which of the silenced genes or combination of silenced genes contribute to the formation of breast cancer. Epigenetic changes like DNA methylation and histone modification play an important role in breast tumorigenesis. DNA methylation are modifications to DNA that regulate whether genes are turned on or off. If the gene is silenced, it is turned off. As part of the diagnosis of suspicious changes in the breast diagnostic imaging is carried out and a needle biopsy is taken. In case ofB3 lesions - lesions ofunce1tain malignant potential, the diagnostic surgical biopsy is performed, otherwise therapeutic surgery is perfonned, which includes tumorectomy or mastectomy and lymph node procedures.

Most diagnostic procedures are performed due to benign changes. Surgery presents distress, unnecessary absence from work, risk of complications, as well as a potentially painful scar and poor aesthetic outcome for patients, so there is a need to find new markers that would help reduce the number of unnecessary surgeries. The prospective clinical trial will include women who will undergo a needle biopsy as part of the Slovenian screening programme and women who will be present at multidisciplinary meeting for unpalpable breast lesions at the Institute of Oncology Ljubljana. We will determine methylation status of genes on a surgical biopsy and access what is the correlation of the methylation status between the surgical biopsy and needle biopsy. For malignant lesions, we will also determine the methylation status of genes in the surrounding tissue. Enrolment will take place from September 2024 to June 2025. It is estimated that 300 patients will be enrolled.