Abstract P3-10-12: Pilot Phase of the Randomized PlanB Trial: Prospective Comparison of Molecular Classification, Oncotype DX® and Clinical-Pathological Characteristics in Hormone-Receptor (HR) Positive Primary Breast Cancer
Authors: Gluz O , Kreipe H , Christgen M , Salem M , Clemens M , Markmann S , Liedtke B , Barinoff J , Aktas B , Henschen S , Lübbe K , Shak S , Baehner R , Liedtke C , Nitz U , Harbeck N 
Published: April 2011

Abstract
Background:
Despite progress in adjuvant breast cancer (BC) treatment, overtreatment due to decisions based on conventional prognostic factors (lymph nodes (LN), grade, tumor size) alone remains an important clinical problem. Recurrence Score®, RS is validated using pre-specified analyses, genes, cutt-offs in several randomized patient collectives as a potent prognostic and predictive marker in HR positive BC. Here, we present the first WSG-Plan B trial preplanned correlation analysis of central grade, nodal status, RS, and luminal A/B subtypes.
Material and Methods: The West German Study Group (WSG) Plan B trial (planned n=2,448) is a randomized Phase-III-trial evaluating anthracyline-free adjuvant chemotherapy (Cht) (6x TC) vs. standard 4xEC-4xDOC in high-risk N0 and N+ HER2-negative BC. In HR+ BC with 0-3 LN, RS is the decision criterion for (&gt;11) or against (≥11) Cht randomization. Tumor blocks are prospectively evaluated by a central pathologist for grade, histology and Ki-67. In HR+ disease, molecular subtypes (luminal A vs. B) are grouped using a Ki-67 cut-off of 13.25% (Cheang et al, JNCI 2009) and 20% (Penault-Llorca et al JCO 2009). Exploratory analysis with Elston-Ellis central grade and Ki-67 based (mitosis measured by Ki-67) grade will be performed. Results: As of June 2010, 1375 patients in 96 centers have been registered and 1067 randomized into Plan B. In 298 patients, RS results and clinical-pathological characteristics were available. In 266 patients complete information on all factors was available (132 N0, 134 N+). RS groups using the pre-specified trial cut-offs of 0-11, 12-25 and &lt;25 were 21%, 59%, and 20%, respectively, with a median of 18. RS groups using the standard cutt-offs (&lt;18/18-30/&gt;30) were 48%, 38%, 14%. Central grade 1, 2, or 3 was observed in 4%, 50%, and 46% of cases. We observed a modest (Spearman) correlation between central grade and RS (e.g 83.8% of G3 tumors with RS &gt;25, rs=0.331, P&lt;0.001), Ki-67 based grade (rs=0.34, P&lt;0.001), and Ki-67 as continuous variable (median 20), (rs=0.438, P&lt;0.001). No significant correlation was observed between nodal groups (0 vs. 1-3 vs. 4+) and RS groups (e.g. RS≥11 in N0/1-3/4+: 17.8%/22.6%/25.0%; p=0.253) Modest correlations were found for luminal A/B subtypes by both Ki-67 cut-off's (13.25%; 20%) and RS groups using our conservative trial cut-off (12/12-25/&gt;25), and guideline-recommended &lt;18/18-30/&gt;30 (see table 1).Discussion:
For the first time, we demonstrate a modest but significant correlation between centrally assed tumor grade, molecular classes by IHC Ki-67 cutt offs, and RS, particularly in the high RS group. However, our data also indicate that there is substantial discordance between the methods and thus an urgent need for optimzing risk-stratification classifiers. Table 1. Association of RS and molecular subtypes

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-12.