Abstract P4-08-05: Prediction of distant recurrence using EndoPredict among women with ER-positive, HER2-negative breast cancer with a maximum follow-up of 16 years
Authors: Filipits M , Dubsky P , Rudas M , Greil R , Balic M , Fitzal F , Bago-Horvath Z , Singer C , Hlauschek D , Kronenwett R , Bernhisel R , Lancaster J , Gnant M 
Published: May 2019

Abstract
Background: EndoPredict has been previously validated as a prognostic test in women with ER-positive, HER2-negative disease who received endocrine therapy only as part of the ABCSG6 and -8 trials. Here, we further evaluate the prognostic value of EndoPredict in this cohort with longer-term follow-up and compare 10-year distant recurrence (DR) and 5-15 years late recurrence according to nodal status.
Methods: This analysis included 1702 patients with ER-positive, HER2-negative disease who received endocrine therapy only. Prognostic value of EPclin score and EPclin risk category (high, low) on the risk of distant recurrence adjusted for patient and disease characteristics was evaluated using multivariable Cox proportional hazard models. Kaplan-Meier estimators were used to estimate DR according EPclin class and were compared using log rank test. Analyses were performed for the overall cohort, by nodal status, and for patients who were distant recurrence free at year 5 (late recurrence).
Results: The median follow-up was 9.6 years (range 0-16.6), an increase of 4.2 years over previous reports. Reanalysis with longer follow-up confirms that EPclin is a significant predictor of DR after adjusting for clinical factors, regardless of nodal status (Table 1). Overall, 62.6% of patients had low risk EPclin scores and 10-year DR was significantly improved relative to those with high risk scores (p&lt;0.0001; Table 2). When nodal status was considered, 77.8% of node negative tumors and 34.9% of node positive (1-3 PLN) tumors had low risk EPclin scores. Regardless of nodal status, DR was significantly improved for those with low versus high risk EPclin scores (Table 2). Similar results were observed for the patients who were DR free at year 5 (5-15 year follow-up) (Table 2).
Conclusion: This reanalysis of previous EndoPredict data with a longer follow-up confirms that EPclin can identify a large group of patients at low risk of distant recurrence after 10 years who might be sufficiently treated with 5 years adjuvant endocrine therapy only, independent of nodal status. Replication of these results for the late distant recurrence between years 5-15 also shows that EPclin scores may also be informative in selecting patients who may safely forgo extended endocrine therapy.
Table 1.Multivariate analysis 0-15 year DR5-15 year DRCohortHR*p-valueHR*p-valueAll patients2.55&lt;0.00012.56&lt;0.0001Node negative1.680.00352.010.00881-3 positive nodes2.68&lt;0.00013.430.0004*Hazard Ratio (HR) per unit score after adjusting for age, tumor grade, Ki67, ER, PR, and treatment
Table 2.DR according to EPclin score Low risk EPclinHigh risk EPclin CohortHR*%0-10 year DR (95% CI)%0-10 year DR (95% CI)Log-rank p-valueAll patients N=17024.7762.60.96 (0.94, 0.97)37.40.80 (0.77, 0.84)&lt;0.0001Node negative N=11653.4777.80.96 (0.94, 0.97)22.20.87 (0.83, 0.92)&lt;0.00011-3 positive nodes N=4533.6534.90.96 (0.92, 0.99)65.10.81 (0.76, 0.87)0.0003CohortHR*%5-15 year DR (95% CI)%5-15 year DR (95% CI)Log-rank p-valueAll patients N=13864.5264.70.96 (0.93, 0.98)35.30.84 (0.79, 0.90)&lt;0.0001Node negative N=9753.7678.30.97 (0.95, 0.99)21.70.85 (0.75, 0.96)&lt;0.00011-3 positive nodes N=3623.0036.50.87 (0.72, 1.00)63.50.84 (0.77, 0.92)0.0337*HR for EPclin high risk versus low risk
Citation Format: Filipits M, Dubsky P, Rudas M, Greil R, Balic M, Fitzal F, Bago-Horvath Z, Singer C, Hlauschek D, Kronenwett R, Bernhisel R, Lancaster J, Gnant M. Prediction of distant recurrence using EndoPredict among women with ER-positive, HER2-negative breast cancer with a maximum follow-up of 16 years [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-05.