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N Engl J Med. 2016 Aug 25;375(8):717-29. doi: 10.1056/NEJMoa1602253.

70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.

Author information

1
From Champalimaud Clinical Center-Champalimaud Foundation, Lisbon, Portugal (F.C.); Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (L.J.V.); European Organization for Research and Treatment of Cancer Headquarters (J.B., L. Slaets, V.G., B.M., K.T.), Breast International Group Headquarters (T.G., C. Straehle), and Institut Jules Bordet, Université Libre de Bruxelles (C. Sotiriou, M.P.), Brussels, and Centre Hospitalier Universitaire Université Catholique de Louvain, Namur (P.V.) - both in Belgium; University of Milan and Istituto Europeo di Oncologia (G.V.) and Europa Donna-European Breast Cancer Coalition (S.K.), Milan, and Azienda Istituti Ospitalieri di Cremona, Cremona (R.P.) - both in Italy; Gustave Roussy, Villejuif (S.D., M.S.), Institut Curie Paris Sciences et Lettres, Université Paris Descartes, Sorbonne Paris Cité, Paris (J.-Y.P.). Institut Curie-Hôpital Rene Huguenin, Saint-Cloud (E.B.), and Centre Georges-Francois-Leclerc, Dijon (S.C.) - all in France; Swiss Institute of Bioinformatics and University of Lausanne, Lausanne, Switzerland (M.D.); Agendia (A.M.G., L. Stork) and the Netherlands Cancer Institute (R.B., E.R.), Amsterdam, Alrijne Ziekenhuis, Rijnland Leiderdorp (P.A.N.), Jeroen Bosch Hospital, 's-Hertogenbosch (T.J.S.), and Medisch Centrum Alkmaar, Alkmaar (J.M.H.) - all in the Netherlands; Institute of Oncology, Ljubljana, Slovenia (E.M.); Evangelisches Krankenhaus Bethesda, Duisburg, Germany (U.N.); University of Texas Health Sciences Center, San Antonio (P.R.); Hospital Universitario Vall d'Hebron, Barcelona (I.T.R.); Imperial College London, London (G.T.); and University of Texas M.D. Anderson Cancer Center, Houston (A.M.T.).

Abstract

BACKGROUND:

The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy.

METHODS:

In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher.

RESULTS:

A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease.

CONCLUSIONS:

Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).

PMID:
27557300
DOI:
10.1056/NEJMoa1602253
[Indexed for MEDLINE]
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