title: Serum NSE, MMP-9 and HER2 extracellular domain are associated with brain metastases in metastatic breast cancer patients: predictive biomarkers for brain metastases?
abstract: Breast cancer (BC) is the second most common cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM. Elevated serum S100ß protein and neuron-specific enolase (NSE) could reflect the brain damages induced by BM. Matrix metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Also, HER2-amplified BC were shown to have a particular tropism for central nervous system (CNS). This study evaluated the correlation of these biomarkers with the presence of BM in metastatic BC patients. In this case-control study, 88 consecutive metastatic BC patients with BM (BM group) treated in our institution (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor marker determination. Patients were matched by age, tumor biology and number of previous metastatic chemotherapy lines to 162 metastatic BC patients without CNS involvement (control group). Serum NSE, MMP-9 and HER2 extracellular domain (ECD) levels were significantly higher in the BM group (p = 0.0051, p = 0.0062 and p = 0.0057, respectively). In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated patients with BM: odds ratios 4.4 (p < 0.001; 95%CI: 1.9-9.6) for HER2 ECD and 3.5 (p = 0.005; 95%CI: 1.5-8.4) for MMP-9. In multivariate analysis, HER2 ECD and NSE serum levels were independent prognostic factors in patients with BM. Serum HER2 ECD and MMP-9 appear to be associated with BM in metastatic BC patients. Their predictive value for BM still needs to be evaluated in further prospective studies.
authors.affiliation: Department of Medical Oncology, Institut Régional Du Cancer Montpellier ICM, Montpellier, France. amelie.darlix@icm.unicancer.fr.
authors.forename: Amélie
authors.initials: A
authors.lastname: Darlix
authors.affiliation: Department of Clinical Research, Clinique Beausoleil, Montpellier, France.|Department of Biology and Oncogenetic, Institut Régional Du Cancer Montpellier ICM, Montpellier, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Lamy
authors.affiliation: Translational Research Unit, Institut Régional Du Cancer Montpellier ICM, Montpellier, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lopez-Crapez
authors.affiliation: Department of Medical Oncology and Radiothérapy, Centre Azuréen De Cancérologie, 1 Place Du Docteur Jean Luc Broquerie, Mougins, France.
authors.forename: Antoine Laurent
authors.initials: AL
authors.lastname: Braccini
authors.affiliation: Department of Medical Oncology, Institut Régional Du Cancer Montpellier ICM, Montpellier, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Firmin
authors.affiliation: Department of Medical Oncology, Institut Régional Du Cancer Montpellier ICM, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Biometrics Unit, Institut Régional Du Cancer Montpellier ICM, Montpellier, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Thézenas
authors.affiliation: Department of Medical Oncology, Institut Régional Du Cancer Montpellier ICM, Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Jacot
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001932:Brain Neoplasms / Q000097:blood / Q000201:enzymology* / Q000556:secondary*; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D020780:Matrix Metalloproteinase 9; D010751:Phosphopyruvate Hydratase; D018719:Erb-b2 Receptor Tyrosine Kinases; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C508053:ERBB2 protein, human; C579270:MMP9 protein, human
keywords: brain metastases; breast cancer; tumor markers