Validation of 70-gene prognosis signature in node-negative breast cancer

J. M. Bueno-De-Mesquita (1) , S. C. Linn (2) , R. Keijzer (3) , J. Wesseling (1) , D. S. A. Nuyten (4) , C. Krimpen (5) , C. Meijers (6) , P. W. Graaf (3) , M. M. E. M. Bos (7) , A. A. M. Hart (4) , E. J. T. Rutgers (8) , J. L. Peterse , H. Halfwerk (9) , R. Groot (1) , A. Pronk (10) , A. N. Floore (11) , A. M. Glas (11) , L. J. Veer (1, 11) , M. J. Vijver (1, 12)

1 Department of Pathology
2 Department of Medical Oncology
3 Department of Surgery
4 Department of Radiotherapy
5 Department of Pathology
6 Department of Pathology
7 Department of Internal Medicine
8 Department of Surgical Oncology
9 Department of Experimental Therapy
10 Department of Pathology
11 Agendia BV
12 Department of Pathology

The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530–536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer ( = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999–2009, 2002;  = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). The 5-year OS was 82 ± 5% in poor (48%) and 97 ± 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2–9.6;  = 0.021). The 5-years DMFP was 78 ± 6% in poor and 98 ± 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6–20;  = 0.007). In the updated series ( = 151; 60% poor vs. 40% good), the 10-year OS was 51 ± 5% and 94 ± 3% (HR 10.7; 95% CI 3.9–30;  < 0.01), respectively. The DMFP was 50 ± 6% in poor and 86 ± 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5–12;  < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.

Mots clés: Gene expression profile; Prognosis signature; Breast cancer; Microarray

J. M. Bueno-De-Mesquita, S. C. Linn, R. Keijzer, J. Wesseling, D. S. A. Nuyten, et al.. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Research and Treatment, 2008, 117 (3), pp.483-495. ⟨10.1007/s10549-008-0191-2⟩. ⟨hal-00478268⟩