Can Pathologic Features and Immunophenotype of ER+, Node Negative Breast Cancers Identify High and Low Risk OncotypeDX Subgroups?
KH Allison, SM Dintzis, PL Kandalaft, AM Gown, LC Goldstein. University of Washington, Seattle, WA; PhenoPath Laboratories, Seattle, WA; IMPRIS, Seattle, WA
Background: The NCCN guidelines currently give consideration to OncotypeDX testing of ER positive, lymph node negative invasive breast cancers to help predict benefit from chemotherapy. However, the test is expensive ($3500) and only those cases resulting in high or low recurrence scores (RS) can affect treatment choices. This study was designed to assess whether pathologic and immunophenotypic characteristics can accurately identify those tumors with either high or low RS.
Design: We retrospectively reviewed 104 cases of ER-positive, node negative breast cancers that had been sent for OncotypeDX testing. All cases were assessed for Nottingham grade as well as semiquantitative immunohistochemical analysis of ER and PR (Allred scores), Ki67-Ag, HER2, cyclin D1, bcl-2, p53 overexpression, and lymphatic invasion (tumor in podoplanin-positive spaces). Analysis was then performed to determine if there were immunophenotypically defined patient subgroups corresponding to the high and low RS subgroups.
Results: Overall, 44 (42%) of cases had low RS, 49 (47%) had intermediate RS and 11 (11%) had high RS. Of 85 ductal carcinomas 9 were high RS, 38 intermediate and 28 low RS. Low grade was significantly associated with low RS (p = 0.0024) and high grade was associated with high RS (p = 0.032). PR > 5 was strongly associated with low RS (p < 0.0001) and PR< 5 was associated with high RS (p = 0.0027). Using a combination of histologic type, grade and PR levels, we identified subgroups of patients with highly predictable RS. 86% (18 of 21) grade 1, PR > 5 ductal carcinomas were low RS and 0 were high RS. In contrast, 83% (5 of 6) grade 3, PR < 5 ductal carcinomas had high RS and 0 were low RS. There was also a strong association between high RS tumors and the presence of lymphatic invasion and p53 overexpression.
Conclusions: Subgroups within ER positive, lymph node negative breast cancers can be defined by tumor grade and immunophenotype that correspond to high and low RS defined by OncotypeDX testing. Determination of these histologic and immunophenotype-defined subgroups could have accurately subclassified 23% of the total cases and avoided $84,000 of OncotypeDX testing.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 25, Tuesday Afternoon