Abstract P2-11-13: The 70-gene signature (70-GS) in a lymph node-negative patient series with intermediate risk 21-gene recurrence scores (RS) and known adjuvant treatment recommendations

Background: Multi-gene assays have informed the treatment of patients (pts) with estrogen receptor positive (ER+) and lymph node negative (LN-) breast cancer (BC). For pts with tumors in the 21-gene RS intermediate range (RS18-30), the benefit of adjuvant chemotherapy (chemo) added to endocrine therapy is uncertain. The 70-GS provides prognostic information by classifying LN+ and LN-, ER+ and ER- tumors as low or high risk though lacks predictive validation in phase III trials. Our primary objective was to perform the 70-GS on a large consecutive series of intermediate RS with known adjuvant treatment recommendations to evaluate the distribution of treatment recommendations by 70-GS risk category. Other objectives were to identify how many pts with intermediate RS are classified by the 70-GS as low or high risk; compare microarray-based assessment of ER, PR, and HER2 with ER, PR and HER2 by conventional immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and the 21-gene RS assay; and to compare clinical subtyping based on ER, PR, HER2 and Ki-67 with the 80-gene molecular subtyping signature. Methods: All consecutive ER+LN- BC cases with an intermediate 21-gene RS obtained at Loyola University Medical Center from 1/2005 - 9/2012 were analyzed. All adjuvant treatment recommendations were made after obtaining the 21-gene RS. The 70-GS, micro-array assessment of ER, PR and HER2, and molecular subtyping were performed on paraffin embedded tumor blocks. Standard descriptive statistical methods were employed. Results: 102 samples were analyzed. The 3 assays were successfully performed in 89 cases. Median RS was 21, range 18-30. 50 (56.2%) samples were 70-GS high risk; 39 (43.8%) were low risk. The table below shows the distribution of adjuvant chemotherapy recommendations made after obtaining the 21-gene RS. Of the 39 pts with low risk 70-GS results, 14 had been recommended chemo. Of the 50 high risk pts, 34 had been recommended no chemo. Concordance of microarray-based assessment of ER with the 21-gene ER test was 54/57 and 85/89 with ER by IHC. Concordance of microarray-based assessment of HER2 with the 21-gene HER2 test was 49/50, 87/89 with HER2 by IHC, and 87/89 by FISH. The 89 ER+HER2- clinical subtypes were re-categorized as 39 luminal A, 48 luminal B, 1 basal and 1 HER2 molecular subtypes. Conclusions: Within the 21-gene RS intermediate range, there is a mix of 70-GS high and low risk results. There is good concordance of microarray-based assessment of ER and HER2 with the 21-gene ER and HER2 test; with ER by IHC, and HER2 by IHC and FISH. The majority of the clinical ER+HER2- cases were categorized as molecular subtypes luminal A and B. The optimal adjuvant treatment recommendation for pts with intermediate RS but either 70-GS high risk or low risk is uncertain. Results of completed phase III prospective studies (TAILORx and MINDACT) will clarify this critical treatment dilemma for patients and their physicians. View this table: Adjuvant Chemotherapy Recommendations in pts with intermediate RS by 70-GS Risk Category Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-13.