PAM50 Risk of Recurrence Score Provides Strongest Prognostic Information for Risk Beyond 5 Years in Estrogen Receptor–Positive Breast Cancer
Adjuvant endocrine therapy beyond 5 years reduces recurrence in patients with estrogen receptor–positive breast cancer. Recent studies from the transATAC cohort have shown that immunohistochemical markers (IHC4), Oncotype DX recurrence score, and PAM50 risk of recurrence score are associated with time to distant recurrence in hormone receptor–positive breast cancer. In a study reported in Journal of the National Cancer Institute, Ivana Sestak, PhD, of Queen Mary University of London, and colleagues assessed the value of these tests when added to clinical treatment score in predicting recurrence at 5 to 10 years in women with estrogen receptor–positive breast cancer. They found that risk of recurrence provided the strongest prognostic information for years 5 to 10.
The study involved analysis of formalin-fixed paraffin-embedded tumor blocks from hormone receptor–positive breast cancers (from the transATAC study) from 940 UK women who constituted a subset of those randomly assigned to the monotherapy groups (tamoxifen or anastrozole alone) in the ATAC trial.
Eligible women had not received chemotherapy and had IHC4, risk of recurrence (PAM50 without tumor size), and Oncotype DX recurrence scores available. Univariate and multivariable proportional hazards models were used to determine the prognostic value of all variables and scores for distant recurrence separately in years 0 to 5 and specifically for years 5 to 10 for all patients.
Multivariate Analyses for 0 to 5 Years
On multivariate analysis, tumor size (χ2 = 10.82, P = .001) and nodal status (χ2 = 11.08, P < .001) were the strongest individual clinical factors for years 0 to 5. Of IHC markers, only progesterone receptor (χ2 = 7.76, P = .005) and Ki67 (χ2 = 6.99, P = .008) added clinically significant information, with similar effect sizes. When added to the clinical treatment score, the most prognostic information in years 0 to 5 was provided by IHC4 (χ2 = 24.89, P < .001), with the recurrence score (χ2 = 13.22, P < .001) and risk of recurrence (χ2 = 11.41, P < .001) scores contributing similar prognostic information.
Multivariate Analyses for Years 5 to 10
Nodal status (χ2 = 21.72, P < .001) and tumor size (χ2 = 10.52, P = .001) were the only individual factors that added prognostic information in years 5 to 10 in the multivariable model. IHC4 (χ2 = 7.41, P = .007) and recurrence score (χ2 = 5.55, P = .02) were relatively weak prognostic factors, whereas risk of recurrence added a substantial amount of prognostic information in the model including clinical treatment score (χ2 = 16.29, P < .001).
Multivariable analyses were performed for distant recurrence for IHC4, recurrence score, and risk of recurrence when added to clinical treatment score in node-negative, node-positive, HER2-negative, node-negative/HER2-negative, and node-positive/HER2-negative subgroups. Risk of recurrence was the only molecular score that added significant prognostic information in all five subgroups.
Among node-negative patients, only risk of recurrence added significant prognostic information (χ2 = 8.83, P = .003). In HER2-negative patients, a substantial amount of prognostic information was added by risk of recurrence (χ2 = 18.18, P < .001) compared with IHC4 (χ2 = 5.67, P = .02) and no significant information was added by recurrence score. In node-negative/HER2-negative patients, risk of recurrence added substantial information (χ2 = 13.85, P < .001) and IHC4 was of borderline significance (χ2 = 3.89, P = .05) In node-positive patients, IHC4 (χ2 = 6.05, P = .01), recurrence score (χ2 = 5.17, P = .02), and risk of recurrence (χ2 = 8.37, P = .004) added information, whereas in node-positive/HER2-negative patients, only risk of recurrence (χ2 = 4.78, P = .03) added significant information.
The investigators concluded, “None of the IHC4 markers provided statistically significant prognostic information in years 5 to 10, except for nodal status and tumor size. [Risk of recurrence] gave the strongest prognostic information in years 5 to 10. These results may help select patients who could benefit most from hormonal therapy beyond 5 years of treatment.
The study was supported by Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation, Royal Marsden NIHR Biomedical Research Centre, Nanostring, and Cancer Research UK.
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