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

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Abstract

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 (n = 315) or ET + CT (n = 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; P = 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; P < 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; P = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17–0.71; P < 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.

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Acknowledgments

This work was supported by the Austrian Society of Surgery and Agendia BV. Both provided unrestricted educational grants for the work of M. Knauer. We are indebted to Femke de Snoo, MD PhD for critically reading the manuscript and providing helpful comments and to Marleen Kok for providing part of the data used for our analyses.

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Authors and Affiliations

  1. Division of Diagnostic Oncology, Netherlands Cancer Institute, Plesmanlaan 121, NL-1066CX, Amsterdam, Netherlands

    Michael Knauer, Stella Mook, Emiel J. T. Rutgers, Michael Hauptmann, Marc J. van de Vijver, Rutger H. T. Koornstra, Jolien M. Bueno-de-Mesquita, Sabine C. Linn & Laura J. van ’t Veer

  2. Department of General and Thoracic Surgery, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria

    Michael Knauer

  3. Agendia Inc., Huntington Beach, CA, USA

    Richard A. Bender

  4. Agendia BV, Amsterdam, Netherlands

    Laura J. van ’t Veer

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  1. Michael Knauer
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Correspondence to Laura J. van ’t Veer.

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Knauer, M., Mook, S., Rutgers, E.J.T. et al. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat 120, 655–661 (2010). https://doi.org/10.1007/s10549-010-0814-2

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  • DOI: https://doi.org/10.1007/s10549-010-0814-2

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