PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)

• Published in: NPJ breast cancer 2016-01, Vol.2 (1), p.15023, Article 15023
• Main Authors: Liu, Minetta C, Pitcher, Brandelyn N, Mardis, Elaine R, Davies, Sherri R, Friedman, Paula N, Snider, Jacqueline E, Vickery, Tammi L, Reed, Jerry P, DeSchryver, Katherine, Singh, Baljit, Gradishar, William J, Perez, Edith A, Martino, Silvana, Citron, Marc L, Norton, Larry, Winer, Eric P, Hudis, Clifford A, Carey, Lisa A, Bernard, Philip S, Nielsen, Torsten O, Perou, Charles M, Ellis, Matthew J, Barry, William T
• Format: Article
• Language: English
• Subjects: 631/67/1347; 631/67/1857; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Biology; Human Genetics; Oncology
• ISSN: 2374-4677; 2374-4677
• DOI: 10.1038/npjbcancer.2015.23

PAM50 intrinsic breast cancer subtypes are prognostic independent of standard clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS) and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy. A significant interaction between intrinsic subtypes and DD-therapy benefit was hypothesized. Suitable tumor samples were available from 1,471 (73%) of 2,005 subjects. Multiplexed gene-expression profiling generated the PAM50 subtype call, proliferation score, and risk of recurrence score (ROR-PT) for the evaluable subset of 1,311 treated patients. The interaction between DD-therapy benefit and intrinsic subtype was tested in a Cox proportional hazards model using two-sided alpha=0.05. Additional multivariable Cox models evaluated the proliferation and ROR-PT scores as continuous measures with selected clinical covariates. Improved outcomes for DD therapy in the evaluable subset mirrored results from the complete data set (RFS; hazard ratio=1.20; 95% confidence interval=0.99–1.44) with 12.3-year median follow-up. Intrinsic subtypes were prognostic of RFS ( P