Factors Predicting Late Recurrence for Estrogen Receptor–Positive Breast Cancer

BACKGROUND: Adjuvant endocrine therapy beyond 5 years reduces recurrence in patients with estrogen receptor–positive breast cancer. We have previously shown that immunohistochemical markers (IHC4) and two gene expression profile tests (recurrence score [RS] and PAM50 risk of recurrence [ROR]) are associated with time to distant recurrence, and we have now assessed the value of each of these scores and routine clinical variables for predicting outcome, specifically in years 5 to 10. METHODS: We used univariate and multivariable proportional hazards models to determine the prognostic value of all variables and scores (IHC4, RS, ROR) for distant recurrence, separately in years 0 to 5 and specifically for years 5 to 10 for all patients. All statistical tests were two-sided. RESULTS: Nodal status and tumor size were at least as strong in years 5 to 10 as in years 0 to 5 (nodal status, years 5–10: χ(2) = 21.72 vs years 0–5: χ(2) = 11.08, both P < .001; tumor size, years 5–10: χ(2) = 10.52 vs years 0–5: χ(2) = 10.82, both P = .001). Ki67 and the overall IHC4 score were the only statistically significant biomarkers related to distant recurrence univariablely in the 5 to 10 year period (χ(2) = 8.67, χ(2) = 13.22, respectively). The ROR score was the strongest molecular prognostic factor in the late follow-up period (χ(2) = 16.29; P < .001), whereas IHC4 (χ(2) = 7.41) and RS (χ(2) = 5.55) were only weakly prognostic in this period. Similar results were seen for all subgroups and for all recurrences. CONCLUSIONS: None of the IHC4 markers provided statistically significant prognostic information in years 5 to 10, except for nodal status and tumor size. ROR 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.