Abstract GS6-04: The EndoPredict score predicts residual cancer burden after neoadjuvant chemotherapy and after neoendocrince therapy in HR+/HER2- breast cancer patients from ABCSG 34
Authors: Dubsky PC , Fesl C , Singer CF , Pfeiler G , Kronenwett R , Hubalek M , Bartsch R , Stoeger H , Pichler A , Petru E , Bjelic-Radisic V , Greil R , Rudas M , Tea M-KM , Wette V , Petzner AL , Sevelda P , Egle D , Fitzal F , Exner R , Jakesz R , Balic M , Tinchon C , Bago-Horvath Z , Lax S , Regitnig P , Gnant M , Filipits M 
Published: February 2018

Background:

In the neoadjuvant treatment setting of ER+/HER2- breast cancer (BC) the choice between preoperative endocrine - (NET) or preoperative chemotherapy (NCT) is largely based on the expression of hormone receptors (HR), grading and possibly Ki-67. The EndoPredict 12-gene molecular score (EP) is a validated prognostic score based on the expression of genes involved in cellular processes including proliferation and ER signaling/differentiation. The application of the EP molecular score may thus provide additional insight into neoadjuvant response of tumors.

Methods:

This prospective translational study was carried out as an exploratory endpoint within the ABCSG 34 protocol (SABCS 2016, Singer et al.) and included only the HR+ subset of women. ABCSG 34 was a randomized 2-arm academic phase-II trial including 400 patients (250 ER+) with HER2 negative early BC. Patients were selected for either NET or NCT according to the study protocol reflecting standard of care: postmenopausal women with ER+++, or ER++ and Ki67 &lt;14%, and G1,2,X tumors received 6 months of Letrozole. Postmenopausal patients with ER-(and PgR+) or ER low and Ki67 ≥14%, and with G3 tumors, and premenopausal patients, received 8 cycles of anthracycline/taxane based chemotherapy. Primary endpoint was Residual Cancer Burden score (RCB0/I vs RCBII/III) at surgery in women with or without Tecemotide (L-BLP25). EP was assessed from diagnostic cores and the predefined risk groups (EP low-risk vs EP high-risk; cutoff value: 5.0) and the score as a continuous variable (EPc) were applied to all patients with both full molecular - and RCB data (n=217).

Results:

134 patients (EP low-risk:9; EP high-risk:125) with HR+ tumors received NCT. Stage I: 14.9%, II/III: 84%; G3: 56%; mean Ki-67: 40.4%. No patient with EP low-risk score showed RCB0/I (NPV: 100%) whereas 26.4% of EP high-risk showed full response. In logistic regression EP as a continuous score (EPc) was a significant predictor of RCB0/I, showed an AUC (95% CI) of 0.736 (0.63 - 0.84) and revealed close correlation with Ki-67.

83 patients (EP low-risk:44; EP high-risk:39) received NET. Stage I: 38.6%, II/III: 60.2%; G3: 4.8%; mean Ki-67: 14.9%. 27.3% (n=12/44) with EP low-risk and 7.7% (n=3/39) with EP high-risk showed RCB0/I. EPc was a significant predictor of RCB0/I with an AUC (95% CI) of 0.726 (0.60 - 0.85). In all multivariate analyses low anatomic stage was the most powerful predictor of RCB0/I.

Conclusions:

Clinical standard of care separated ABCSG 34 patients into two HR+ cohorts with differing clinical features and treated distinctly with either NET or NCT: In women treated with neoadjuvant Letrozole a high molecular score indicated a very low possibility of endocrine response. In women clinically selected for neoadjuvant chemotherapy, a high EP score was associated with a higher probability of chemotherapy response and the low EP risk group outlined a group of women with very poor tumor response to NCT(NPV 100%).

In summary, EP low risk is associated with tumor response to endocrine treatment and predicts resistance in the chemotherapy group. NCT, especially to attain breast conservation in ER+/HER2-/EP low risk should be reconsidered.

Citation Format: Dubsky PC, Fesl C, Singer CF, Pfeiler G, Kronenwett R, Hubalek M, Bartsch R, Stoeger H, Pichler A, Petru E, Bjelic-Radisic V, Greil R, Rudas M, Tea M-KM, Wette V, Petzner AL, Sevelda P, Egle D, Fitzal F, Exner R, Jakesz R, Balic M, Tinchon C, Bago-Horvath Z, Lax S, Regitnig P, Gnant M, Filipits M. The EndoPredict score predicts residual cancer burden after neoadjuvant chemotherapy and after neoendocrince therapy in HR+/HER2- breast cancer patients from ABCSG 34 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS6-04.