PurposeEndoPredict (EPclin) is a prognostic test validated to inform decisions on adjuvant chemotherapy to endocrine therapy alone for patients with oestrogen receptor-positive, HER2-negative breast cancer. Here, we determine the performance of EPclin for estimating 10-year distant recurrence-free interval (DRFI) rates for those who received adjuvant endocrine therapy (ET) alone compared to those with chemotherapy plus endocrine therapy (ET+C).MethodsA total of 3746 women were included in this joint analysis. 2630 patients received 5years of ET alone (ABCSG-6/8, TransATAC) and 1116 patients received ET+C (GEICAM 2003-02/9906). The primary objective was to evaluate the ability of EPclin to provide an estimate of the 10-year DR rate as a continuous function of EPclin separately for ET alone and ET+C. Cox proportional hazard models were used for these analyses.ResultsEPclin was highly prognostic for DR in women who received ET alone (HR 2.79 (2.49-3.13), P<0.0001) as well as in those who received ET+C (HR 2.27 (1.99-2.59), P<0.0001). Women who received ET+C had significantly smaller increases in 10-year DR rates with the increasing EPclin score than those receiving ET alone (EPclin=5; 12% ET+C vs. 20% ET alone). We observed a significant positive interaction between EPclin and treatment groups (P-(interaction)=0.022).ConclusionsIn this comparative non-randomised analysis, the rate of increase in DR with EPclin score was significantly reduced in women who received ET+C versus ET alone. Our indirect comparisons suggest that a high EPclin score can predict chemotherapy benefit in women with ER-positive, HER2-negative disease.