Abstract S3-01: EndoPredict (EPclin) score for estimating residual distant recurrence (DR) risk in ER+/HER2- breast cancer (br ca) patients treated with 5 years adjuvant endocrine therapy alone: Validation and comparison with the oncotype DX recurrence score (RS)
Authors: Dowsett M , Sestak I , Buus R , Kronenwett R , Denkert C , Krappmann K , Scheer M , Petry C , Dubsky P , Cuzick J 
Published: May 2016

Background: RS is widely used for estimating 10-yr risk of DR for br ca patients receiving 5yrs adjuvant endocrine treatment alone. EndoPredict is a prognostic test which unlike RS combines its eight-gene expression signature (EP score) with tumor size and nodal status to provide the EPclin score with a single low/high risk cut-off at 10% risk of DR at 10yrs similar to the low/intermediate risk cut-off with RS.

Aims: To determine the prognostic value of EP/EPclin over 10yrs, 0-5yrs and 5-10yrs in ER+/HER2- br ca patients and to compare this with the RS (i) alone (primary objective) and (ii) in addition to the clinical treatment score (CTS [developed in TransATAC]: nodes (N); tumour size; grade; age; tam or AI).

Methods: mRNA from 928 ER+/HER2- primary br ca from patients treated with anastrozole or tamoxifen in the ATAC trial on which RS was already available were assessed for the EP/EPclin. Primary end point was DR. Kaplan–Meier and Cox regression analyses were used to determine DR risk for 0-10, 0-5 and 5-10yrs follow-up. Likelihood ratio tests (LR-chi sq) were used to assess the prognostic information provided by EP, EPclin, and RS alone and in combination with CTS.

Results: Median follow-up was 9.95 yrs. The table shows the LR-chi sq for the prognostic information provided by each marker alone (univariate) and the information on top of CTS for all patients, and N- and N+ subgroups in 0-10, 0-5 and 5-10yrs. EP and EPclin provided substantially more prognostic information than RS across all three time periods and subgroups, except for N- patients in 0-5yrs. EP and EPclin also provided more information in addition to CTS than RS in 0-10yrs due to better performance of EP and EPclin in 5-10yrs where RS added no significant information to CTS. Using predefined cut-offs, EPclin and RS identified 546 (58.8%) and 573 (61.7%) patients as low risk respectively (HR (95%CI) low vs. non-low risk: 5.9 (3.9-9.1) and 2.7 (1.9-3.8), respectively). The EP score significantly added prognostic information to the RS over 0-10yrs and 5-10yrs in the overall, N- and N+ populations. Cases classified discordantly by EPclin and RS followed the EPclin classification more closely than RS classification.

Prognostic information from EP, EPClin, RSLR-chi-sqAll patientsNode-negativeNode-positiveUnivariate0-10yrs0-5; 5-10yrs0-10yrs0-5; 5-10yrs0-10yrs0-5; 5-10yrsEP49.325.7; 23.630.811.9; 15.614.57.9; 6.6EPclin139.380.0; 59.340.017.0; 22.748.332.2; 16.1RS29.126.1; 5.621.318.7; 4.88.08.0; 1.0CTS149.885.0; 64.735.619.0;16.961.635.2; 26.3added to CTS      EP16.46.9; 9.815.55.2; 6.68.32.3; 3.4EPClin20.310.5; 9.917.03.6; 9.05.46.4; 2.3RS12.811.8; 2.318.78.1; 1.44.13.7; 0.7LR-chi sq &gt;3.8, p&lt;0.05

Conclusions: EPclin was highly prognostic for DR in all patients, N-, N+, early and late metastasis. EPclin provided more prognostic information than RS in part but not solely because of the integration of the EP score with N and tumour size parameters. The data stress the importance of including clinicopathological factors in deriving an overall estimate of risk.

Citation Format: Dowsett M, Sestak I, Buus R, Kronenwett R, Denkert C, Krappmann K, Scheer M, Petry C, Dubsky P, Cuzick J. EndoPredict (EPclin) score for estimating residual distant recurrence (DR) risk in ER+/HER2- breast cancer (br ca) patients treated with 5 years adjuvant endocrine therapy alone: Validation and comparison with the oncotype DX recurrence score (RS). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S3-01.