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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Minetta C Liu, Brandelyn N Pitcher, Elaine R Mardis, Sherri R Davies, Paula N Friedman, Jacqueline E Snider, Tammi L Vickery, Jerry P Reed, Katherine DeSchryver, Baljit Singh, William J Gradishar, Edith A Perez, Silvana Martino, Marc L Citron, Larry Norton, Eric P Winer, Clifford A Hudis, Lisa A Carey, Philip S Bernard, Torsten O Nielsen, Charles M Perou, Matthew J Ellis, William T Barry

ABSTRACT

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 < 0.0001) irrespective of treatment assignment. No subtype-specific treatment effect on RFS was identified (interaction P = 0.44). Proliferation and ROR-PT scores were prognostic for RFS (both P < 0.0001), but no association with treatment benefit was seen (P = 0.14 and 0.59, respectively). Results were similar for OS. The prognostic value of PAM50 intrinsic subtype was greater than estrogen receptor/HER2 immunohistochemistry classification. PAM50 gene signatures were highly prognostic but did not predict for improved outcomes with DD anthracycline- and taxane-based therapy. Clinical validation studies will assess the ability of PAM50 and other gene signatures to stratify patients and individualize treatment based on expected risks of distant recurrence. More... »

PAGES

npjbcancer201523

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/npjbcancer.2015.23

DOI

http://dx.doi.org/10.1038/npjbcancer.2015.23

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1045473711

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28691057


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