Metaplastic breast cancer (MpBC) is a heterogeneous disease and is characterized by the differentiation of the neoplastic epithelium into squamous cells and/or mesenchymal elements. MpBC is rare but very aggressive and presents high rates of recurrence, poor survival outcomes, and poor response to current chemotherapies optimized for other breast cancer subtypes. To date, there are no established treatments for MpBCs, due to paucity of clinical trials and near absence of preclinical models for investigation. In the last years we developed a unique resource of 6 MpBCs Patient-derived xenograft (PDX), which are suitable models to evaluate the clinical diversity of MpBC. Those models are being used for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. The aim of this study was to evaluate and compare the different population of MpBCs by combining spatial resolution mRNA and protein expression profiles (Nanostring GeoMx Digital Spatial Profiler).
We evaluated the mRNA expression of over 1,800 genes and a panel of 80 proteins/phospho-proteins in 3 MpBC primary tumors and matched PDX samples. We evaluated at least 6 different populations per sample using Formalin-fixed, paraffin-embedded (FFPE) tissue and identified the molecular profile of every cell population inter and intra samples.
Our preliminary results indicate that pathways related to MAPK, PI3K/AKT/mTOR and EMT signaling are disrupted in MpBC, but not in every cell population. Based on the PanCk levels we were able to identify population that presented lower PanCK expression and alteration in Phospho-JNK (T183/Y185), Phospho-AKT1 (S473), Phospho-c-RAF (S338) and Phospho-AKT (phospho T308) levels.
Considering that MpBC remains a deadly disease, a better understanding of its cell population heterogeneity will allow the identification of targets and combination of targets with potential to be translated to the clinic.
McGill University.
Fonds de Recherche du Québec - Santé (FRQS), Canadian Cancer Society (CCS).
All authors have declared no conflicts of interest.