The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer

Michael Knauer (1, 2) , Stella Mook (1) , Emiel J. T. Rutgers (1) , Richard A. Bender (3) , Michael Hauptmann (1) , Marc J. Vijver (1) , Rutger H. T. Koornstra (1) , Jolien M. Bueno-De-Mesquita (1) , Sabine C. Linn (1) , Laura J. Veer (1, 4)

1 Division of Diagnostic Oncology
2 Department of General and Thoracic Surgery
3 Agendia Inc.
4 Agendia BV

Multigene assays have been developed and validated to determine the prognosis of breast cancer. In this study, we assessed the additional predictive value of the 70-gene MammaPrint signature for chemotherapy (CT) benefit in addition to endocrine therapy (ET) from pooled study series. For 541 patients who received either ET ( = 315) or ET + CT ( = 226), breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) at 5 years were assessed separately for the 70-gene high and low risk groups. The 70-gene signature classified 252 patients (47%) as low risk and 289 (53%) as high risk. Within the 70-gene low risk group, BCSS was 97% for the ET group and 99% for the ET + CT group at 5 years with a non-significant univariate hazard ratio (HR) of 0.58 (95% CI 0.07–4.98;  = 0.62). In the 70-gene high risk group, BCSS was 81% (ET group) and 94% (ET + CT group) at 5 years with a significant HR of 0.21 (95% CI 0.07–0.59;  < 0.01). DDFS was 93% (ET) versus 99% (ET + CT), respectively, in the 70-gene low risk group, HR 0.26 (95% CI 0.03–2.02;  = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17–0.71;  < 0.01). Results were similar in multivariate analysis, showing significant survival benefit by adding CT in the 70-gene high risk group. A significant and clinically meaningful benefit was observed by adding chemotherapy to endocrine treatment in 70-gene high risk patients. This benefit was not significant in low risk patients, who were at such low risk for recurrence and cancer-related death, that adding CT does not appear to be clinically meaningful.

Mots clés: Breast cancer; Gene expression profiling; Adjuvant chemotherapy; Risk assessment

Michael Knauer, Stella Mook, Emiel J. T. Rutgers, Richard A. Bender, Michael Hauptmann, et al.. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Research and Treatment, 2010, 120 (3), pp.655-661. ⟨10.1007/s10549-010-0814-2⟩. ⟨hal-00535448⟩