Analysing the immunohistochemical and molecular genetic features of metaplastic breast carcinomas with the main goal to define a new and more clinically and biologically significant taxonomy system for these lesions.

Metaplastic carcinoma

Metaplastic breast carcinoma is an umbrella descriptive term that encompasses tumours composed of a complex mixture of usual types of breast carcinomas and metaplastic elements, such as squamous and spindle cells, cartilage and bone. Although several classification systems for these tumours have been put forward, there is no international consensus as to which classification should be used. Moreover, most of these systems are solely based on the morphological features, without any molecular support for the categorisation. Most importantly, the prognostic impact of the subcategorisation of metaplastic breast carcinomas is rather controversial.

We have recently demonstrated that regardless of the histological type, >90% of these tumours immunohistochemically express myoepithelial/ basal-like features. In collaboration with Professor Christopher D. M. Fletcher, Brigham and Women’s Hospital, Harvard Medical School, USA, Professor Jahn Nesland, The Norwegian Radium Hospital, Norway, and Professor Fernando Schmitt, Institute of Molecular Pathology and Immunology, University of Porto, Portugal, we have been analysing the immunohistochemical and molecular genetic features of these lesions and will compare them with those of other types of breast cancer, including basal-like carcinomas.

We have recently demonstrated that up to 70% of metaplastic breast carcinomas harbour EGFR overexpression and that EGFR gene amplifications may be the underlying genetic mechanism in one third of the cases. Given that tumours harbouring EGFR gene activating mutations and/ or amplification respond to specific tyrosine kinase inhitors, our findings suggest that EGFR may be a novel therapeutic target for these lesions.

Our main goal is to define a new and more clinically and biologically significant taxonomy system for these lesions and identify novel therapeutic targets for these chemotherapy-resistant tumours.