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

François Bertucci⁹  Frédérique Penault-Llorca³  Daniel Birnbaum⁶  Patrice Viens⁹  Mario Campone²  Anne-Laure Martin⁴  Emmanuelle Charafe-Jauffret⁹  Pascal Finetti⁶  Fabrice Andre⁷  Pierre Kerbrat¹  Daniel Serin^1,10  Benjamin Esterni⁸  Henri Roche⁵  Jean-Marie Boher⁸  Jocelyne Jacquemier⁶ 

[1] Department of Medical Oncology, Centre Eugène Marquis, Rue de la Bataille Flandre-Dunkerque, Rennes, 35042, France;Department of Medical Oncology, Centre René Gauducheau, Bd Jacques Monod, Saint-Herblain, 44805, France;Department of Pathology, Centre Jean Perrin, 58, rue Montalembert, Clermont-Ferrand, 63011, France;Fédération Nationale des Centres de Lutte Contre le Cancer, 101, rue de Tolbiac, Paris, 75654, France;Department of Medical Oncology, Institut Claudius Régaud, 20/24, rue du Pont-Saint-Pierre, Toulouse, 31052, France;Department of Molecular Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, 232, Bd Ste-Marguerite, Marseille, 13009, France;Department of Medical Oncology, Institut Gustave Roussy, 114 rue Edourad Vaillant, Villejuif, 94805, France;Department of Biostatistics, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, 232, Bd Ste-Marguerite, Marseille, 13009, France;UFR of Medicine, Aix-Marseille University, 58 bd Charles Livon, Marseille, 13001, France;Department of Medical Oncology, Institut Sainte-Catherine, 1750 Chemin Lavarin, Avignon, 84000, France

关键词: molecular subtypes;    Ki67;    breast cancer;    adjuvant docetaxel;   

Others  :  799140
DOI  :  10.1186/bcr3051

 received in 2011-05-10, accepted in 2011-11-01,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Jacquemier et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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