PAM50 Risk of Recurrence Score Helps Predict Late Distant Recurrence After 5 Years of Endocrine Treatment for Breast Cancer
In a combined analysis of outcomes in the translational research cohort of the Arimidex, Tamoxifen Alone or in Combination trial (TransATAC) and the Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG 8) trial reported in the Journal of Clinical Oncology, Sestak and colleagues found that the PAM50 risk of recurrence score added prognostic information to clinical treatment score for late distant recurrence of breast cancer after 5 years of endocrine treatment.
Study Details
The study involved long-term follow-up data and tissue samples from 2,137 postmenopausal women with hormone receptor–positive early-stage breast cancer who received endocrine therapy in the ABCSG 8 and TransATAC trials and did not have a recurrence within the first 5 years after diagnosis. The ATAC trial compared anastrozole vs tamoxifen for 5 years, and the ABCSG8 trial compared 5 years of tamoxifen vs 2 years of tamoxifen followed by 3 years of anastrozole.
The prognostic value of the PAM50-based risk of recurrence score was assessed for recurrence beyond 5 years. The clinical treatment score, which was developed from the TransATAC data set, contains information on nodal status, tumor size, grade, age, and treatment. Median follow-up in the analysis was 10 years.
Performance in All Patients
Patients in risk of recurrence– low-, intermediate-, and high-risk groups (based on 10-year distant recurrence risk of < 10%, 10%–20%, and > 20%) had risks of distant recurrence during 5 to 10 years of 2.4%, 8.3% (hazard ratio [HR] = 3.26 vs low-risk), and 16.6% (HR = 6.90 vs low-risk).
Among all patients, clinical treatment score added more prognostic information for distant recurrence beyond 5 years in both univariable analysis (likelihood ratio [LR] χ2 = 94.12) and when added to the risk of recurrence score in bivariable analysis (LR χ2 = 61.43). The risk of recurrence score added significant prognostic information, but less than the clinical treatment score, in both univariable (LR χ2 = 67.94) and bivariable analysis (LR χ2 = 35.25). Hazard ratios (all significant) were 1.96 for clinical treatment score and 2.69 for risk of recurrence on univariable analysis and 1.80 and 2.07 on bivariable analysis.
Node-Negative Patients
Among 1,580 node-negative patients, the risk of recurrence score added more prognostic information than the clinical treatment score in both univariable (LR χ2 = 30.95 vs 21.48) and bivariable analyses (LR χ2 = 17.25 vs 7.79), with similar outcome observed among those patients with node-negative/HER2-negative disease (n = 1,455). Hazard ratios (all significant) for clinical treatment score and risk of recurrence were 1.96 and 2.56 on univariable analysis and 1.56 and 2.11 on bivariable analysis among all node-negative patients and 2.12 and 3.00 on univariable analysis and 1.65 and 2.41 on bivariable analysis among node-negative/HER2-negative patients. Among node-negative/HER2-negative patients, HRs were 5.49 for risk of recurrence–high-risk and 3.75 for risk of recurrence–intermediate-risk groups vs the risk of recurrence–low-risk group.
Node-Positive Patients
Among 557 women with node-positive tumors, the clinical treatment score added more prognostic information on both univariable (LR χ2 = 35.60) and bivariable analyses (LR χ2 = 25.67), with the risk of recurrence score adding significant but reduced prognostic information. HRs (all significant) for clinical treatment score and risk of recurrence were 1.84 and 2.52 on univariable analysis and 1.74 and 2.15 on bivariable analysis.
The correlation between clinical treatment score and risk of recurrence was weak (r = 0.36). For clinical treatment score vs risk of recurrence, 53.3% vs 55.4% of patients were categorized as low risk, 32.4% vs 25.2% as intermediate risk, and 14.3% vs 19.5% as high risk.
The investigators concluded: “The risk of recurrence score added clinically meaningful prognostic information to the clinical treatment score in all patients and all subgroups in the late follow-up period. These results suggest that the risk of recurrence score may be helpful for separating patients into risk groups who could be spared or potentially benefit from extended hormonal therapy beyond 5 years of treatment.”
Ivana Sestak, PhD, of Queen Mary University London, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Breakthrough Breast Cancer, National Institute for Health Research Biomedical Research Centre at The Royal Marsden Hospital, and a grant from Cancer Research United Kingdom. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
