Research article
Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC - PACS 01 randomized trial
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* Corresponding author: François Bertucci bertuccif@marseille.fnclcc.fr
1 Department of BioPathology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, 232, Bd Ste-Marguerite, Marseille, 13009, France
2 Department of Molecular Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, 232, Bd Ste-Marguerite, Marseille, 13009, France
3 Department of Biostatistics, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, 232, Bd Ste-Marguerite, Marseille, 13009, France
4 Department of Medical Oncology, Institut Claudius Régaud, 20/24, rue du Pont-Saint-Pierre, Toulouse, 31052, France
5 Department of Medical Oncology, Institut Sainte-Catherine, 1750 Chemin Lavarin, Avignon, 84000, France
6 Department of Medical Oncology, Centre Eugène Marquis, Rue de la Bataille Flandre-Dunkerque, Rennes, 35042, France
7 Department of Medical Oncology, Institut Gustave Roussy, 114 rue Edourad Vaillant, Villejuif, 94805, France
8 UFR of Medicine, Aix-Marseille University, 58 bd Charles Livon, Marseille, 13001, France
9 Fédération Nationale des Centres de Lutte Contre le Cancer, 101, rue de Tolbiac, Paris, 75654, France
10 Department of Medical Oncology, Centre René Gauducheau, Bd Jacques Monod, Saint-Herblain, 44805, France
11 Department of Medical Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, 232, Bd Ste-Marguerite, Marseille, 13009, France
12 Department of Pathology, Centre Jean Perrin, 58, rue Montalembert, Clermont-Ferrand, 63011, France
Breast Cancer Research 2011, 13:R109 doi:10.1186/bcr3051
See related editorial by Perez-Garcia and Cortes, http://breast-cancer-research.com/content/14/1/104
Published: 1 November 2011Abstract
Introduction
The PACS01 trial has demonstrated that a 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's 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 to 0.92, P = 0.013), and Ki67-positivity (HR = 1.53; 95% CI 1.12 to 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 to 0.79 for Ki67-positive versus HR = 1.10, 95% CI 0.75 to 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 to 1.84); the reduction in the relapse risk was 53% (HR = 0.47, 95% CI 0.22 to 1.01), 34% (HR = 0.66, 95% CI 0.37 to 1.19), and 12% (HR = 0.88, 95% CI 0.49 to 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.