Breast cancer (BC) is the most frequent tumor in woman, representing 20-30% of all malignancies and continues being the first reason of death for cancer in European women. Triple negative (TN) BC present minor survival rates than other BC subtypes. Key reasons for that is the absence of predictive markers of response to current therapy and the absence of targeted therapies. This study aims to identify proteins with predictive value of central Nervous System (CNS) metastases and therapeutic target candidates.
This is a case-control retrospective study comparing patients (pts) with metastases to CNS vs pts without them after adjuvant treatment. Sample selection included 50 samples. Formalin-fixed, paraffin-embedded samples were retrieved from Hospital 12 de Octubre Biobank. Proteins were quantified by parallel reaction monitoring.
The average age was 55 years (range 25-85). Forty-seven pts (88.67%) had ductal histology and presented high grade tumors (40 pts; 75.47%). Eight women in the case group presented as first distant recurrence CNS (34.80%), local recurrence (3pts, 13.04%), lung (2pt; 8.7%), bone (1pt; 4.34%) and other locations (7pts; 30.38%). In the control group, first distant recurrence occurred locally (6pts; 46.1%), bone (2pts; 15.4%), lung (1pt; 7.7%) and other sites (4pts; 23.1%). Protein expression data was successfully obtained from 50 samples. ISG15 ubiquitin-like modifier, (P05161) was overexpressed in triple negative breast cancer tumors that develop metastases to CNS (p = 0.036) compared to tumors that do not develop these CNS metastases.
TN tumors frequently metastasize to visceral organs, particularly lungs and brain, and are less likely to metastasize to bone. The interferon-stimulated gene 15 ubiquitin-like modifier (ISG15) encodes an IFN-inducible, ubiquitin-like protein. The ISG15 protein is involved in numerous cellular functions, including interferon-induced immune responses and the regulation of cellular protein turnover. Therefore, ISG15 may represent a novel breast tumor marker helpful in selecting pts who will develop CNS metastases. It also should be explored as a therapeutic target in this clinical context.
Clinical trial identification
Legal entity responsible for the study
Biomedica Molecular Medicine SL.
L. Trilla-Fuertes: Employee of Biomedica Molecular Medicine SL. A. Gámez, J.A. Fresno: Shareholders in Biomedica Molecular Medicine SL. All other authors have declared no conflicts of interest.