title: BreastPRS is a gene expression assay that stratifies intermediate-risk Oncotype DX patients into high- or low-risk for disease recurrence.
abstract: Molecular prognostic assays, such as Oncotype DX, are increasingly incorporated into the management of patients with invasive breast carcinoma. BreastPRS is a new molecular assay developed and validated from a meta-analysis of publically available genomic datasets. We applied the assay to matched fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tumor samples to translate the assay to FFPE. A linear relationship of the BreastPRS prognostic score was observed between tissue preservation formats. BreastPRS recurrence scores were compared with Oncotype DX recurrence scores from 246 patients with invasive breast carcinoma and known Oncotype DX results. Using this series, a 120-gene Oncotype DX approximation algorithm was trained to predict Oncotype DX risk groups and then applied to series of untreated, node-negative, estrogen receptor (ER)-positive patients from previously published studies with known clinical outcomes. Correlation of recurrence score and risk group between Oncotype DX and BreastPRS was statistically significant (P < 0.0001). 59 of 260 (23 %) patients from four previously published studies were classified as intermediate-risk when the 120-gene Oncotype DX approximation algorithm was applied. BreastPRS reclassified the 59 patients into binary risk groups (high- vs. low-risk). 23 (39 %) patients were classified as low-risk and 36 (61 %) as high-risk (P = 0.029, HR: 3.64, 95 % CI: 1.40-9.50). At 10 years from diagnosis, the low-risk group had a 90 % recurrence-free survival (RFS) rate compared to 60 % for the high-risk group. BreastPRS recurrence score is comparable with Oncotype DX and can reclassify Oncotype DX intermediate-risk patients into two groups with significant differences in RFS. Further studies are needed to validate these findings.
authors.affiliation: Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, 525 East 68th Street, Starr 1031E, New York, NY 10065, USA. tid9007@med.cornell.edu
authors.forename: Timothy M
authors.initials: TM
authors.lastname: D'Alfonso
authors.forename: Ryan K
authors.initials: RK
authors.lastname: van Laar
authors.forename: Linda T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: Wasay
authors.initials: W
authors.lastname: Hussain
authors.forename: Rachel
authors.initials: R
authors.lastname: Flinchum
authors.forename: Nathan
authors.initials: N
authors.lastname: Brown
authors.forename: Linda Saint
authors.initials: LS
authors.lastname: John
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D016612:Paraffin Embedding; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors