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uPA/PAI-1, Oncotype DX™, MammaPrint® Valeurs pronostique et prédictive pour une utilité clinique dans la prise en charge du cancer du sein

uPA/PAI-1, Oncotype DX™, MammaPrint® Prognosis and predictive values for clinical utility in breast cancer management

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Oncologie

Résumé

Introduction

Dans le cancer du sein, le développement des marqueurs biologiques pronostiques ou prédictifs a pour objectif de mieux identifier les patientes pour lesquelles un traitement par chimiothérapie pourrait être évité ou a contrario indiqué. Dans ce contexte, en 2009, l’Institut national du cancer (INCa), agence sanitaire et scientifique de l’État chargée de coordonner les actions de lutte contre le cancer, avait publié en partenariat avec la Société française de sénologie et de pathologie mammaire un rapport sur l’état des connaissances relatives aux biomarqueurs uPA/PAI-1, Oncotype DX™ et MammaPrint® dans la prise en charge du cancer du sein. Ce rapport avait montré que seule la valeur pronostique d’uPA/PAI-1 atteignait le plus haut niveau de preuve (LOE I selon la grille de Hayes 1998). En 2012, devant la parution de nouvelles publications et la divergence des messages diffusés sur les signatures moléculaires, il a été décidé d’actualiser le rapport de 2009. Cet article présente les principales conclusions accompagnées de leurs niveaux de preuve.

Méthode

Le processus de mise à jour s’est appuyé sur l’analyse des données publiées depuis la recherche bibliographique de 2009, complétée par l’avis d’un groupe de travail multidisciplinaire indépendant. Les niveaux de preuve employés sont ceux de la classification définie par Simon en 2009 (grille de Hayes 1998 après mise à jour): LOE IA et LOE IB: niveau de preuve élevé; LOE IIB and LOE IIC: niveau de preuve intermédiaire; LOE IIIC and LOE IV-VD.: niveau de preuve faible.

Conclusions

Chez les patientes pN0, uPA/PAI-1, marqueurs d’invasion, ont un niveau de preuve élevé (LOE IA selon Simon) pour la valeur pronostique de la survie sans récidive à 10 ans. Il reste à confirmer leur valeur prédictive de réponse aux anthracyclines. Aucune donnée médicoéconomique sur uPA/PAI-1 n’a pu être identifiée. Pour Oncotype DX™ et MammaPrint®, les valeurs pronostique et prédictive n’ont pas atteint à ce jour le niveau de preuve LOE I. Ce travail confirme les niveaux de preuve précédemment établis dans le rapport de 2009. Par ailleurs, les données ne permettent pas de conclure à une valeur ajoutée de ces deux tests par rapport aux outils existants. Les données médicoéconomique ne permettent pas de statuer sur le rapport coût/efficacité des stratégies utilisant ces tests dans la décision thérapeutique compte tenu d’un niveau de qualité insuffisant pour la plupart des études et d’une forte incertitude mise en évidence par les quelques études bien menées. En pratique, au-delà des niveaux de preuve attribuables à la valeur pronostiqu et prédictive d’un biomarqueur, l’utilité clinique d’un nouveau marqueur dans l’aide à la prescription d’une chimiothérapie repose sur sa valeur ajoutée par rapport aux marqueurs validés (RH, HER2 et les marqueurs de prolifération comme Ki67) et aux critères anatomocliniques. Puisqu’ils sont les seuls marqueurs validés à témoigner du processus d’invasion, uPA/PAI-1 peuvent apporter une information complémentaire et donc avoir une valeur ajoutée par rapport aux marqueurs existants. Les données de la littérature manquent pour apprécier le poids de cette valeur ajoutée dans la décision de prescrire ou non une chimiothérapie.

Abstract

Context and Aims

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 « Société française de sénologie et de pathologie mammaire » 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. No data were identified on uPA/PAI-1 medico-economic value. 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.

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Authors and Affiliations

  1. Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandoeuvre-lès-Nancy Cedex, France

    E. Luporsi

  2. CHRU, 1 place de l’Hôpital, 67000, Strasbourg, France

    J. P. Bellocq

  3. Centre Antoine Lacassagne, 33 avenue de Valombrose, 06189, Nice, France

    J. Barrière

  4. Institut Gustave Roussy, 114 rue Edouard-Vaillant, 94805, Villejuif Cedex, France

    J. Bonastre & C. Mazouni

  5. Institut d’histopathologie, 55 rue Amiral du Chaffault, 44100, Nantes, France

    J. Chetritt

  6. UMR 912 INSERM, Institut Paoli-Calmettes, 232 Bd Ste Marguerite, 13009, Marseille, France

    A. G. Le Corroller

  7. Hôpital Saint-Louis, 1 avenue Claude-Vellefaux, 75010, Paris, France

    P. de Cremoux

  8. Faculté de Médecine-Secteur Nord, Chemin des Bourrely, AP-HM, Marseille, 13915, Marseille cedex 20, France

    F. Fina & P. M. Martin

  9. CHU Grenoble, 29 avenue Maquis du Grésivaudan, 38701, La Tronche, France

    A. S. Gauchez

  10. Institut Régional du Cancer, 208 avenue des Apothicaires, Montpellier Cedex 5, France

    P. J. Lamy & G. Romieu

  11. Centre Oscar Lambret, 3 rue Frédéric Combemale, 59000, Lille, France

    J. P. Peyrat

  12. Institut National du Cancer, 52 avenue André Morizet, 92513, Boulogne-Billancourt Cedex, France

    L. Verdoni, V. Mazeau-Woynar & D. Kassab-Chahmi

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  1. E. Luporsi
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Correspondence to D. Kassab-Chahmi.

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Luporsi, E., Bellocq, J.P., Barrière, J. et al. uPA/PAI-1, Oncotype DX™, MammaPrint® Valeurs pronostique et prédictive pour une utilité clinique dans la prise en charge du cancer du sein. Oncologie 16, 196–206 (2014). https://doi.org/10.1007/s10269-014-2379-x

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