title: Serum HER2 extra-cellular domain, S100ß and CA 15-3 levels are independent prognostic factors in metastatic breast cancer patients.
abstract: Metastatic breast cancer (MBC) prognosis is highly variable, depending on various factors such as the biological subtype, the performance status, disease extension…. A better evaluation of a patient's prognostic factors could allow for a more accurate choice of treatments. The role of serum tumor markers remains, however, unclear in this population. Considering the recent interest in phenotypic changes and tumor heterogeneity during breast cancer progression, additional tumor markers could be interesting in this setting.
  
  
  
  Two hundred fifty MBC patients treated at the Montpellier Cancer Institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples. The usual MBC clinical and pathological variables were collected, altogether with Cancer Antigen 15-3 (CA15-3), Carcinoembryonic Antigen (CEA), HER2 extra-cellular domain (ECD), Neuron Specific Enolase (NSE), S100ß protein and Matrix Metalloproteinase 9 (MMP-9) serum levels in order to determine their prognostic value.
  
  
  
  With a median follow-up of 40.8 months, median overall survival was 16.2 months (95 % CI 12.4-20.6). In multivariate analysis, the performance status, brain or subcutaneous metastases, the number of previous metastatic chemotherapy lines and the tumor biological subtype were independent prognostic factors. Elevated CA 15-3 (HR = 1.95, IC 95 % 1.31-2.93, p = 0.001), HER2 ECD (regardless of tumor HER2 status, HR = 2.51, IC 95 % 1.53-4.12, p < 0.001) and S100ß (HR = 1.93, IC 95 % 1.05-3.54, p = 0.033) serum levels were independently associated with a poor outcome.
  
  
  
  Serum CA 15-3, HER2 ECD and S100ß could represent useful independent prognostic factors in MBC. Of particular interest is the independent value of serum HER2 ECD levels, regardless of the tumor HER2 status, possibly linked to metastatic tumor heterogeneity.
authors.affiliation: Department of Medical Oncology, Institut régional du Cancer de Montpellier, 208 rue des apothicaires, 34298, Montpellier, France. amelie.darlix@icm.unicancer.fr.
authors.forename: Amélie
authors.initials: A
authors.lastname: Darlix
authors.affiliation: Department of Clinical Research, Clinique Beausoleil, 19 Avenue de Lodève, 34070, Montpellier, France.|Department of Biology and Oncogenetic, Institut régional du Cancer de Montpellier, 208 rue des apothicaires, 34298, Montpellier, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Lamy
authors.affiliation: Translational Research Unit, Institut régional du Cancer de Montpellier, 208 rue des apothicaires, 34298, Montpellier, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lopez-Crapez
authors.affiliation: Centre Azuréen de Cancérologie, 1 place du Docteur Jean Luc Broquerie, 06250, Mougins, France.
authors.forename: Antoine Laurent
authors.initials: AL
authors.lastname: Braccini
authors.affiliation: Department of Medical Oncology, Institut régional du Cancer de Montpellier, 208 rue des apothicaires, 34298, Montpellier, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Firmin
authors.affiliation: Department of Medical Oncology, Institut régional du Cancer de Montpellier, 208 rue des apothicaires, 34298, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Biometrics unit, Institut régional du Cancer de Montpellier, 208 rue des apothicaires, 34298, Montpellier, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Thezenas
authors.affiliation: Department of Medical Oncology, Institut régional du Cancer de Montpellier, 208 rue des apothicaires, 34298, Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Jacot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009362:Neoplasm Metastasis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D016019:Survival Analysis
chemical_list: D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D064568:S100 Calcium Binding Protein beta Subunit; C060192:MUC1 protein, human; C579160:S100B protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; Matrix metalloproteinase 9; Metastases; Neuron-specific enolase; S100ß; Serum HER2; Tumor heterogeneity; Tumor markers