Ki67 EXPRESSION AND DOCETAXEL EFFICACY IN RECEPTOR PSITIVE PATIENTS

J Clin Oncol. 2009 Apr 20. [Epub ahead of print]

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Ki67 Expression and Docetaxel Efficacy in Patients With Estrogen Receptor-Positive Breast Cancer.

Penault-Llorca F, André F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V, Jacquemier J, Baranzelli MC, Bibeau F, Antoine M, Lagarde N, Martin AL, Asselain B, Roché H.

Department of Pathology, Centre Jean Perrin, Clermont-Ferrand; Department of Medicine and Translational Research Unit, Institut Gustave Roussy, Villejuif; Department of Pathology, Centre Hospitalier Universitaire, Nantes; Departments of Pathology and Medical Oncology, Institut Claudius Regaud, Toulouse; Department of Pathology, Centre François Baclesse, Caen; Department of Pathology, Centre Paul Papin, Angers; Department of Pathology, Institut Paoli-Calmettes, Marseille; Department of Pathology, Centre Oscar Lambret, Lille; Department of Pathology, Centre Val d'Aurelle, Montpellier; Department of Pathology, Centre Hospitalier Universitaire Tenon; Fédération Nationale des Centres de Lutte Contre le Cancer; Department of Biostatistics, Institut Curie, Paris; and Department of Pathology, Centre Hospitalier Universitaire Brest, Brest, France.

PURPOSE: The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) -positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. PATIENTS AND METHODS: Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. RESULTS: Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). CONCLUSION: Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.