title: Characterisation of the triple negative breast cancer phenotype associated with the development of central nervous system metastases.
abstract: OBJECTIVE
  Breast cancer (BC) is the most frequent tumour in women, representing 20-30% of all malignancies, and continues to be the leading cause of cancer deaths among European women. Triple-negative (TN) BC biological aggressiveness is associated with a higher dissemination rate, with central nervous system (CNS) metastases common. This study aims to elucidate the association between gene expression profiles of PTGS2, HBEGF and ST6GALNAC5 and the development of CNS metastases in TNBC.
  
  
  METHODS
  This is a case-controlled retrospective study comparing patients (pts) with CNS metastases versus patients without them after adjuvant treatment. The selection of the samples was performed including 30 samples in both case and control groups. Formalin-fixed, paraffin-embedded samples were retrieved from the Hospital 12 de Octubre Biobank. Five 10 µm sections from each FFPE sample were deparaffinised with xylene and washed with ethanol, and the RNA was then extracted with the RecoverAll Kit (Ambion). Gene expression was assessed using TaqMan assays.
  
  
  RESULTS
  A total of 53 patients were included in the study. The average age was 55 years (range 25-85). About 47 patients (88.67%) had ductal histology and presented high grade (III) tumours (40 patients; 75.47%). Eight women in the case group presented first distant recurrence in the CNS (34.80%), local recurrence (three patients, 13.04%), lungs (two patients; 8.7%), bone (one patient; 4.34%) and other locations (seven patients; 30.38%). In the control group, first distant recurrence occurred locally (six patients; 46.1%), in bone (two patients; 15.4%), lungs (one patient; 7.7%) and other sites (four patients; 23.1%). RNA was successfully obtained from 53 out of 60 samples. PTGS2, HBEGF, and ST6GALNAC5 expression values were not related to metastasis location.
  
  
  CONCLUSIONS
  TN tumours frequently metastasise to the visceral organs, particularly lungs and brain, and are less common in bone. The literature suggests that expression of the three genes of interest (PTGS2, HBEGF, and ST6GALNAC5) could be different in TNBC patients with CNS metastasis when compared to patients without it. We did not find a differential expression pattern in PTGS2, HBEGF, and ST6GALNAC5 genes in primary TNBC showing CNS metastases. Further studies are needed to clarify the role of these genes in CNS metastases in TNBC patients.
authors.affiliation: Department of Medical Oncology, Hospital 12 de Octubre, Av. de Córdoba, s/n, 28041, Spain.
authors.forename: Katerin Rojas
authors.initials: KR
authors.lastname: Laimito
authors.affiliation: I+D Department, Biomedica Molecular Medicine, CLAID building, Campus de Cantoblanco, Calle Faraday, 7, Madrid 28049, Spain.
authors.forename: Angelo
authors.initials: A
authors.lastname: Gámez-Pozo
authors.affiliation: Department of Medical Oncology, Hospital 12 de Octubre, Av. de Córdoba, s/n, 28041, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sepúlveda
authors.affiliation: Department of Medical Oncology, Hospital 12 de Octubre, Av. de Córdoba, s/n, 28041, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Manso
authors.affiliation: Molecular Oncology and Pathology Lab, INGEMM, Hospital La Paz, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: López-Vacas
authors.affiliation: Department of Medical Oncology, Hospital 12 de Octubre, Av. de Córdoba, s/n, 28041, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Pascual
authors.affiliation: Molecular Oncology and Pathology Lab, INGEMM, Hospital La Paz, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Fresno Vara
authors.affiliation: Department of Medical Oncology, Hospital 12 de Octubre, Av. de Córdoba, s/n, 28041, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ciruelos
keywords: breast cancer; central nervous system; metastases; triple negative