Identifying clinically relevant prognostic subgroups in node-positive postmenopausal HR+ early breast cancer patients treated with endocrine therapy: A combined analysis of 2,485 patients from ABCSG-8 and ATAC using the PAM50 risk of recurrence (ROR) score and intrinsic subtype.

Breast Cancer - HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - HER2/ER
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 506)
Michael Gnant, Mitchell Dowsett, Martin Filipits, Elena Lopez-Knowles, Richard Greil, Marija Balic, John W Cowens, Torsten O. Nielsen, Carl Shaper, Ivana Sestak, Christian Fesl, Jack M. Cuzick, Austrian Breast and Colorectal Cancer Study Group; Comprehensive Cancer Center, Department of Surgery, Medical University of Vienna, Vienna, Austria; The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom; Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; The Royal Marsden NHS Foundation Trust, London, United Kingdom; Universitätsklinikum der PMU, Salzburg, Austria; Medical University Graz, Graz, Austria; Nanostring, Seattle, WA; British Columbia Cancer Agency, Vancouver, BC, Canada; MyRAQA Inc., Redwood Shores, CA; Queen Mary, University of London, London, United Kingdom; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, London, United Kingdom

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Abstract Disclosures


Background: Most postmenopausal women with node positive HR+ EBC receive adjuvant chemotherapy. We hypothesized that a molecular-based characterization of residual risk after endocrine therapy using the ROR score and IS may identify node-positive patient subgroups with limited long-term recurrence risk after endocrine therapy better than clinical-pathological risk assessment by clinical treatment score (CTS) alone. Methods: Long-term follow-up and tissue samples were obtained from 2,485 postmenopausal HR+ patients from the ABCSG-8 (N=1,478) and transATAC (N=1,007) trials. The PAM50 test was conducted on RNA extracted from paraffin blocks using the NanoString nCounter Analysis system. The ability of ROR, IS and ROR-defined risk groups (ROR-RG) to add prognostic information to CTS was assessed by the likelihood ratio test in a prospectively defined analysis plan. Results: Patients in the combined data set were grouped by the number of positive nodes into 1 (N1), 2 (N2), or 2 or 3 (N2-3),Baseline hazards for these subgroups were similar in the two trials. ROR score, IS and ROR-RG added statistically significant prognostic information (10-year distant recurrence risk) beyond CTS in all groups. In patients with one positive node, the absolute 10-year risk of distant recurrence was 6.6% [95% CI: 3.3%-12.8%] in the PAM-50-low risk group (40% of patients) and 8.4 % [5.3%-13.3%] in the Luminal A subgroup (69% of patients). Conclusions: The results of this combined analysis demonstrate that a significant proportion of N1 EBC patients have very limited long term recurrence risk and suggest the same for some N2 patients. The PAM50 ROR score, IS and ROR-RG reliably provide additional prognostic information beyond CTS and may be useful in deciding which women with node-positive HR+ EBC can be spared adjuvant chemotherapy.

N1 (N=331)
N2 (N=145)
N2-3 (N=212)
ΔLR χ2 P value ΔLR χ2 P value ΔLR χ2 P value
ROR 17.53 <0.0001 12.18 0.0005 14.16 0.0002
IS 12.16 0.0005 7.80 0.0052 8.58 0.0034
ROR-RG 11.32 <0.004 7.95 <0.02 13.15 <0.001