Background: ER+/HER2− negative (ER+) breast cancers have a proclivity for late recurrence. A first step to an improved adjuvant treatment of late metastasis is to identify women at risk and understand the underlying biology. Several prognostic multigene tests have been developed for ER+ breast cancer patients. Some of these tests have been validated to predict early recurrence events. However, few gene expression assays have been shown to predict late metastases. Here, we assess whether the prognostic EndoPredict (EP) score, which incorporates both the expression levels of proliferative - and ESR1-related genes, can be used to identify late relapse events in ER+ breast cancer patients. Methods: Patients included in this study participated in the ABCSG-6 (tamoxifen-only arm) or ABCSG-8 phase III adjuvant trial and received either tamoxifen for 5 years or tamoxifen for 2 years followed by anastrozole for 3 years. All 1702 ER+/HER2− breast cancer patients were retrospectively assigned into risk categories based on the EP and on common clinical parameters. The primary endpoint was distant metastasis. Ongoing collection of follow-up events allowed estimation of metastasis rates using the Kaplan–Meier method in an early and late time cohort: 0–5 years/early recurrence and 5–10 years/late recurrence. Results: 49% of all patients were classified as low-risk according to the EP score. Kaplan Meier analysis demonstrated that the EP low-risk group had a significantly improved clinical outcome in the first (0–5 years; p Conclusions: The EndoPredict test identified a subgroup of patients that have a low likelihood of developing late metastases. The eight genes contained in the test provide complimentary prognostic information to clinico-pathologic parameters. Both the expression of proliferative - and ESR1-related genes contributes to the underlying biology of late distant metastases. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S4-3.