Adenoid cystic carcinoma of the breast: Molecular profiling updates and multidimensional detection of MYB

Abstract

Adenoid cystic carcinoma (AdCC) of the breast is a rare and distinctive subset of breast cancer that presents significant diagnostic challenges due to its histological diversity and poorly defined molecular traits. AdCC is characterized by the MYB-NFIB fusion, which leads to MYB overexpression and activation of oncogenic downstream pathways, constituting a key disease mechanism. Fluorescence in situ hybridization (FISH) to detect MYB rearrangement has become a critical tool for diagnosing this tumor. However, emerging evidence suggests MYB activation in breast AdCC occurs through multiple mechanisms beyond MYB rearrangements, with several recurrently mutated genes contributing to tumorigenesis. This molecular heterogeneity challenges the diagnostic reliability of FISH-based MYB testing alone. For clinical researchers and practitioners dealing with breast AdCC, a current and thorough understanding of its molecular attributes and diagnostic approaches is essential. This review synthesizes recent advances in breast AdCC molecular genetics, encompassing MYB/MYBL1 rearrangements or amplifications, NOTCH pathway gene mutations, and chromatin remodeling gene alterations. We critically evaluate contemporary methodologies for MYB assessment and discuss their clinical implications.

Keywords: Adenoid cystic carcinoma; Fluorescence in situ hybridisation (FISH); MYB; NOTCH.