title: [uPA/PAI-1, Oncotype DX™, MammaPrint(®). Prognosis and predictive values for clinical utility in breast cancer management].
abstract: OBJECTIVE
  Breast cancer prognosis and predictive biomarkers development would allow sparing some patients from chemotherapy or identifying patients for whom chemotherapy would be indicated. In this context, in 2009, the French National Cancer Institute, a National Health and Science Agency dedicated to cancer, in collaboration with the French society of senology and breast pathology (SFSPM) published a report on the assessment of the prognostic and the predictive clinical validity of tissular biomarkers, uPA/PAI-1, Oncotype DX™ and MammaPrint(®), in breast cancer management. They concluded that only the uPA/PAI-1 prognosis value reached the highest level of evidence (LOE I according to Hayes 1998 classification). In 2012, it was decided to update this report since new data have emerged and because information disparities among clinicians have been identified. This article aims to present the main conclusions together with the levels of evidence associated with those conclusions.
  
  
  METHODS
  The updating process was based on literature published since 2009 appraisal and on multidisciplinary and independent experts' opinion. The levels of evidence (LOE) used are those of the classification defined by Simon in 2009 (updated Hayes 1998 classification): LOE IA and LOE IB: high level of evidence; LOE IIB and LOE IIC: intermediate level of evidence; LOE IIIC and LOE IV-VD: low level of evidence.
  
  
  CONCLUSIONS
  Among patients without lymph-node involvement, uPA/PAI-1, invasion process biomarkers, reach the highest level of evidence for 10 years recurrence free survival prognosis (LOE IA according to Simon). The predictive value to anthracyclins chemotherapy remains to be confirmed. Oncotype DX™ and MammaPrint(®) prognosis and predictive value do not reach the LOE I level. This updating' process confirms the 2009 levels of evidence for all the three biomarkers prognosis value. Besides, concerning Oncotype DX™ and MammaPrint(®), new data do not allow to conclude neither to their complementary clinical information to other clinicopathological existing biomarkers nor to a favorable cost-efficiency ratio in therapeutic decision making and this because of the methodological weakness and uncertainty that are identified in the selected studies. Practically, beyond the prognosis and predictive biomarkers validity, the clinical utility of a new biomarker for chemotherapy indication depends on its clinical added information with regard to validated biomarkers (HR, HER2 and Ki67) and to clinicopathological parameters. Since they are the sole validated biomarkers of the invasion process, uPA/PAI-1 could complete clinical information of other clinicopathological factors and consequently could confer an added clinical value. However, data concerning the impact of this information on chemotherapy clinical indication are lacking.
authors.affiliation: CHRU, 1, place de l'Hôpital, 67000 Strasbourg, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bellocq
authors.affiliation: Institut de cancérologie de Lorraine, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy cedex, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Luporsi
authors.affiliation: Centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Barrière
authors.affiliation: Institut Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Bonastre
authors.affiliation: Institut d'histopathologie, 55, rue Amiral-du-Chaffault, 44100 Nantes, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Chetritt
authors.affiliation: UMR 912 Inserm, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France.
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Le Corroller
authors.affiliation: Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: de Crémoux
authors.affiliation: Faculté de médecine-Secteur Nord, AP-HM de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fina
authors.affiliation: CHU de Grenoble, 29, avenue Maquis-du-Grésivaudan, 38701 La Tronche, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gauchez
authors.affiliation: Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt cedex, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Kassab-Chahmi
authors.affiliation: Institut régional du cancer, 208, avenue des Apothicaires, 34298 Montpellier cedex 5, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Lamy
authors.affiliation: Institut Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Martin
authors.affiliation: Institut Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France.
authors.forename: Chafika
authors.initials: C
authors.lastname: Mazouni
authors.affiliation: Centre Oscar-Lambret, 3, rue Frédéric-Combemale, 59000 Lille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Peyrat
authors.affiliation: Institut régional du cancer, 208, avenue des Apothicaires, 34298 Montpellier cedex 5, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt cedex, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Verdoni
authors.affiliation: Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt cedex, France. Electronic address: recommandations@institutcancer.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Mazeau-Woynar
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005602:France; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D009361:Neoplasm Invasiveness; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011379:Prognosis; D015203:Reproducibility of Results; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator
keywords: Biomarkers; Biomarqueurs; Breast cancer; Cancer du sein; Levels of evidence; Niveaux de preuve; Predictive value; Prognosis; Valeur pronostique; Valeur prédictive