Genetic differences between benign phyllodes tumors and fibroadenomas revealed through targeted next generation...

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Breast fibroepithelial lesions encompass benign fibroadenomas (FAs) and rarer phyllodes tumors (PTs).
• Accurate differentiation between these biphasic tumors is crucial for appropriate patient management.

Purpose of the Study:

• To genetically characterize breast fibroepithelial lesions using a 16-gene panel.
• To identify key mutations that differentiate benign fibroadenomas from benign phyllodes tumors.

Main Methods:

• Analysis of 628 breast fibroepithelial lesions (262 conventional FAs, 45 cellular FAs, 321 benign PTs).
• Utilized a previously curated 16-gene panel for comprehensive sequencing.
• Compared mutation profiles between FAs and benign PTs.

Main Results:

• Benign PTs exhibited a higher mutation burden and more cancer driver gene alterations than FAs.
• MED12, TERT promoter, RARA, FLNA, SETD2, RB1, and EGFR alterations were more frequent in benign PTs.
• TERT promoter alterations demonstrated the highest accuracy in discriminating between FAs and benign PTs.

Conclusions:

• Genetic sequencing and analysis of specific mutations can aid in refining the diagnosis of breast fibroepithelial lesions.
• TERT promoter alterations are a key distinguishing feature between fibroadenomas and benign phyllodes tumors.