Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC - PACS 01 randomized trial.

Jocelyne Jacquemier (1) , Jean-Marie Boher (1) , Henri Roche (2, 1) , Benjamin Esterni (1) , Daniel Serin (3) , Pierre Kerbrat (4) , Fabrice Andre (5) , Pascal Finetti (1) , Emmanuelle Charafe-Jauffret (1) , Anne-Laure Martin (6) , Mario Campone (7) , Patrice Viens (1) , Daniel Birnbaum (1) , Frédérique Penault-Llorca (8) , François Bertucci (1)

1 CRCM / U891 Inserm - Centre de Recherche en Cancérologie de Marseille
2 Département d'oncologie médicale
3 Service d'oncologie médicale
4 Service d'oncologie médicale
5 IGR - Institut Gustave Roussy
6 FNCLCC
7 Service d'oncologie médicale
8 Service de pathologie

ABSTRACT: INTRODUCTION: The PACS01 trial has demonstrated that docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS) and overall survival of node-positive early breast cancer (EBC). We searched for prognostic and predictive markers for docetaxel benefit. METHODS: Tumor samples from 1.099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry. The prognostic and predictive values of each marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing, and triple-negative) were tested. RESULTS: Progesterone receptor-negativity (HR=0.66; 95%CI 0.47-0.92, P=0.013), and Ki67-positivity (HR=1.53; 95%CI 1.12-2.08, P=0.007) were independent adverse prognostic factors. Out of the 34 proteins, only Ki67-positivity was associated with DFS improvement with docetaxel addition (adjusted HR=0.51, 95%CI 0.33-0.79 for Ki67-positive versus HR=1.10, 95%CI 0.75-1.61 for Ki67-negative tumors, P for interaction=0.012). Molecular subtyping predicted the docetaxel benefit, but without providing additional information to Ki67 status. The luminal A subtype did not benefit from docetaxel (HR=1.16, 95%CI 0.73-1.84); the reduction in the relapse risk was 53% (HR=0.47, 95%CI 0.22-1.01), 34% (HR=0.66, 95%CI 0.37-1.19), and 12% (HR=0.88, 95%CI 0.49-1.57) in the luminal B, HER2-overexpressing, and triple-negative subtypes, respectively. CONCLUSIONS: In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy, the most powerful predictor of docetaxel benefit is Ki67-positivity.

Mots clés: adjuvant docetaxel; breast cancer; Ki67; molecular subtypes

Domaines: Cancer

Jocelyne Jacquemier, Jean-Marie Boher, Henri Roche, Benjamin Esterni, Daniel Serin, et al.. Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC - PACS 01 randomized trial.. Breast Cancer Research, 2011, 13 (6), pp.R109. ⟨10.1186/bcr3051⟩. ⟨inserm-00647247⟩