Jean-Pierre Bellocq1, Elisabeth Luporsi2, Jérôme Barrière3, Julia Bonastre4, Jérôme Chetritt5, Anne-Gaëlle Le Corroller6, Patricia de Crémoux7, Frédéric Fina8, Anne-Sophie Gauchez9, Diana Kassab-Chahmi10, Pierre-Jean Lamy11, Pierre-Marie Martin4, Chafika Mazouni4, Jean-Philippe Peyrat12, Gilles Romieu11, Laetitia Verdoni10, Valérie Mazeau-Woynar13. 1. CHRU, 1, place de l'Hôpital, 67000 Strasbourg, France. 2. Institut de cancérologie de Lorraine, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy cedex, France. 3. Centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France. 4. Institut Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. 5. Institut d'histopathologie, 55, rue Amiral-du-Chaffault, 44100 Nantes, France. 6. UMR 912 Inserm, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France. 7. Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France. 8. Faculté de médecine-Secteur Nord, AP-HM de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France. 9. CHU de Grenoble, 29, avenue Maquis-du-Grésivaudan, 38701 La Tronche, France. 10. Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt cedex, France. 11. Institut régional du cancer, 208, avenue des Apothicaires, 34298 Montpellier cedex 5, France. 12. Centre Oscar-Lambret, 3, rue Frédéric-Combemale, 59000 Lille, France. 13. Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt cedex, France. Electronic address: recommandations@institutcancer.fr.
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 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.
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 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.
Keywords:
Biomarkers; Biomarqueurs; Breast cancer; Cancer du sein; Levels of evidence; Niveaux de preuve; Predictive value; Prognosis; Valeur pronostique; Valeur prédictive