BreastPRS Prognostic Score Is Comparable to Oncotype DX Recurrence Score
Ryan van Laar, Timothy M D'Alfonso, Rachel Flinchum, Nathan Brown, Linda Saint John, Sandra J Shin. Signal Genetics, LLC, New York, NY; Weill Cornell Medical College, New York, NY
Background: BreastPRS (Signal Genetics) is a new molecular characterization assay developed and validated from a meta-analysis of publically available genomic datasets. BreastPRS is unique in that the 200 genes utilized in its algorithm (validated in a large series of breast cancer patients) were significantly associated with recurrence free survival, independent of traditional prognostic variables including age, tumor grade, ER status, tumor size, and nodal involvement (J Mol Diagn 2011;13:297-304). One of the criticisms of the widely used Oncotype DX (Genomic Health) assay is that the 21 gene signature largely consists of genes for which surrogate (less expensive and more expedient) means such as immunohistochemistry (e.g. ER, Ki-67) can be used to evaluate their expression. Also, the Oncotype DX assay stratifies patients into 3 risk groups where the benefit of adjuvant chemotherapy in the intermediate risk group is uncertain. In contrast, BreastPRS is a binary assay which stratifies patients into low and high risk groups. In this study, we sought to correlate BreastPRS prognostic score with known Oncotype DX recurrence score (ODxRS) as well as clinicopathogic features in breast cancer patients.
Design: 307 patients with invasive breast cancer and known ODxRS performed as part of their routine clinical care were identified in our files. Unstained formalin-fixed paraffin embedded slides from representative tumor blocks were used for gene array analysis. RNA was isolated after manual microdissection from tissue slides using Prelude FFPA RNA Isolation Module (NuGen). The isolated RNA was converted to cDNA, amplified, and then hybridized to Affymetrix 133 Plus 2.0 Whole Genome microarray. Results were analyzed using the Signal Genetics ResultsPX platform and R (www.r-project.org). The BreastPRS prognostic score was compared with known clinicopathologic variables (age, tumor size, nodal status, ER/PR/HER-2 status, Ki-67, lymphovascular invasion) and ODxRS for each patient.
Results: The correlation of the recurrence score and assignment to a risk group (ODxRs: High, Intermediate, or Low; BreastPRS: High or Low) generated by the BreastPRS and Oncotype DX was statistically significant (P<0.001). In comparison to the ODxRS, the BreastPRS prognostic score also showed stronger association with tumor grade, presence of lymphovascular invasion, and Ki67 index.
Conclusions: The BreastPRS recurrence score is comparable to ODxRS and therefore, may have similar prognostic value in this clinical setting. Prospective studies would be necessary to confirm this observation.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 36, Wednesday Morning