Medline ® Abstract for Reference 6
of 'Adjuvant chemotherapy for HER2-negative breast cancer'
West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment.
Gluz O, Nitz UA, Christgen M, Kates RE, Shak S, Clemens M, Kraemer S, Aktas B, Kuemmel S, Reimer T, Kusche M, Heyl V, Lorenz-Salehi F, Just M, Hofmann D, Degenhardt T, Liedtke C, Svedman C, Wuerstlein R, Kreipe HH, Harbeck N
J Clin Oncol. 2016;34(20):2341.
PURPOSE: The 21-gene Recurrence Score (RS) assay is a validated prognostic/predictive tool in early hormone receptor-positive breast cancer (BC); however, only a few prospective outcome results have been available so far. In the phase III PlanBtrial, RS was prospectively used to define a subset of patients who received only endocrine therapy. We present 3-year outcome data and concordance analysis (among biomarkers/RS).
PATIENTS AND METHODS: Central tumor bank was established prospectively from PlanB (intermediate and high-risk, locally human epidermal growth factor receptor 2-negative BC). After an early amendment, HR-positive, pN0-1 patients with RS≤11 were recommended to omit chemotherapy.
RESULTS: From 2009 to 2011, PlanB enrolled 3,198 patients with a median age of 56 years; 41.1% had node-positive and 32.5% grade 3 disease. In 348 patients (15.3%), chemotherapy was omitted based on RS≤11. After 35 months median follow-up, 3-year disease-free survival in patients with RS≤11 and endocrine therapy alone was 98% versus 92% and 98% in RS>25 and RS 12 to 25 in chemotherapy-treated patients, respectively. Nodal status, central and local grade, the Ki-67 protein encoded by the MKI67 gene, estrogen receptor, progesterone receptor, tumor size, and RS were univariate prognostic factors for disease-free survival; only nodal status, both central and local grade, and RS were independent multivariate factors. Histologic grade was discordant between central and local laboratories in 44%. RS was positively but moderately correlated with the Ki-67 protein encoded by the MKI67 gene and grade and negatively correlated with progesterone receptor and estrogen receptor.
CONCLUSION: In this prospective trial, patients with enhanced clinical risk and omitted chemotherapy on the basis of RS≤11 had excellent 3-year survival. The substantial discordance observed between traditional prognostic markers and RS emphasizes the need for standardized assessment and supports the potential integration of standardized, well-validated genomic assays such as RS with clinicopathologic prognostic factors for chemotherapy indication in early hormone receptor-positive BC.
Oleg Gluz, Ulrike A. Nitz, Ronald E. Kates, Daniel Hofmann, Cornelia Liedtke, Rachel Wuerstlein, and Nadia Harbeck, West German Study Group; Oleg Gluz and Ulrike A. Nitz, Evangelical Hospital Bethesda, Moenchengladbach; Matthias Christgen and Hans H. Kreipe, Medical School Hannover, Hannover; Michael Clemens, Mutterhaus der Borromäerinnen, Trier; Stefan Kraemer, University Clinics Cologne, Cologne; Bahriye Aktas, University Clinics Essen; Sherko Kuemmel, Clinics Essen-Mitte, Essen; Toralf Reimer, Clinics Suedstadt, Rostock; Manfred Kusche, Marienhospital Aachen, Aachen; Volker Heyl, Asklepios Paulinen Clinics; Fatemeh Lorenz-Salehi, Dr Horst-Schmidt Clinics, Wiesbaden; Marianne Just, Oncologic Practice, Bielefeld; Tom Degenhardt, Rachel Wuerstlein, and Nadia Harbeck, University of Munich, Munich; Cornelia Liedtke, University Hospital Schleswig-Holstein Campus Luebeck, Luebeck, Germany; and Steven Shak and Christer Svedman, Genomic Health, Redwood City, CA. firstname.lastname@example.org.