PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)
Year: 2016
Type: article
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.
Source: npj Breast Cancer
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
Institutions: Mayo Clinic, Duke University, Duke Medical Center, Washington University in St. Louis, Alliance for Clinical Trials in Oncology, University of Chicago, NYU Langone Health, New York University, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Mayo Clinic in Florida, Angeles Clinic and Research Institute, Northwell Health, Hofstra University, Memorial Sloan Kettering Cancer Center, Harvard University, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, University of Utah, Huntsman Cancer Institute, University of British Columbia
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,790
Awards: Alliance Statistics and Data Management Center, G1545560008, G1784070713, G1814228702, G1857622882, G2064543036, G2304626200, G2350719019, G2647518335, G2679961467, Support for Specimen Banking in ACOSOG, G36541222, G4040562365, G4185274752, Biological Breast Cancer Classification by qRT-PCR, North Central Cancer Treatment Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group Operations Office, Alliance for Clinical Trials in Oncology Operations Center, G964706321, G973482110
OpenAlex ID: W2226110706