Abstract P4-08-07: Correlation of Oncotype Dx Recurrence Score and Luminal Subtypes of Breast Cancer
Authors: S Henderson, X-J Xie, Y Peng, D Euhus, M Leitch, R Rao, B Haley, V. Sarode
Journal: Cancer Research (2010)

Abstract Background: Molecular subtypes of breast cancer have been characterized by gene expression analysis. Luminal subtypes are hormone receptor (HR) positive and Her2/neu negative. Immunohistochemistry (IHC) has been used as a surrogate test for gene expression. Ki67 is a proliferation marker that identifies high-risk subtype of luminal breast cancer. Recently, the proposed Ki67 index (KI) of 14% was suggested as a cut-off to distinguish between luminal A and luminal B tumors (JNCI. 2009;101:736-750). The oncotype dx (ODx) is a 21- gene test that provides prognostic and predictive information in early stage HR-positive breast cancer patients. The test is reported as low (&amp;lt;18), intermediate (18-30) and high (&amp;gt;30) risk recurrence scores (RS) Design: We investigated the relationship between ODx RS and luminal subtypes of breast cancers using the KI of 14% as the cut-off for distinguishing luminal A and B tumors. Biomarker analysis (ER, PR, Her2/neu, Ki67 and p53) was performed as part of the diagnostic work-up using standard IHC procedures. Scoring was done by automated image analysis. Her2/neu FISH was performed on all IHC 2+ and 3 + results. Pathologic parameters such as, tumor size, grade, and presence of LVI were evaluated. Ploidy was performed by the Autocyte system (Tripath) on Feulgen stained paraffin sections. Results: We identified 106 patients with HR positive breast cancer who were tested for ODx from February 2006 to May 2010. 85/106 had Ki67 data available for analysis. 46/85 (54%) were luminal A and 39/85 (46%) luminal B tumors. The mean KI in luminal A was 6.93% versus 31.1% in luminal B (P&amp;lt;0.0001). The mean tumor size was 1.94 and 1.92 cm in luminal A and B respectively. Grade 1, 2 and 3 comprised 28/85 (32.9%), 49 (57.6%) and 8 (9.41%) of all tumors respectively. Of the grade1 tumors, 75% were luminal A, and grade 3 tumors were predominantly luminal B (p=0.013). LVI was present in 16 cases, 11 (68.8%) in luminal B and 5/16 (31.2%) in luminal A tumors (p=0.0416). Luminal A tumors were predominantly diploid 30/45 (66.6%) and luminal B were mostly aneuploid 21/32 (65.6%) (p=0.019). The overall mean RS in luminal A and B tumors was 14.67 and 20.15 respectively (P&amp;lt;0.0004). Luminal A tumors had low RS in 32/46 (66.6%). and luminal B tumors had predominantly intermediate/high RS in 23/39 (62.1%) (p=0.0082). ER Allred Scores were 7.1 and 7.3 and percent positivity was 88.1% and 91% respectively for luminal A and B subtypes. PR Allred scores were 5.6 and 5.8, and percent positivity was 62.1 and 52.9% for A and B tumors respectively. Information regarding treatment was available in 72 cases. 19 (26.3%) were treated by a combination of chemo and anti-hormonal therapy and 53 (73.6%) were treated by anti hormonal therapy alone, 8 of the 19 (42.1%) luminal A patients received combination therapy versus 11 (57.8%) in the luminal B category (p=0.277). Conclusion: Ki67 is a useful marker that showed significant correlation with RS by ODx. Luminal A tumors are more likely to be low grade, diploid with low RS compared to luminal B tumors. Ki67 in conjunction with other pathologic parameters may serve as a surrogate marker for the ODx RS. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-07.