Background: The Clinical Treatment Score post-5 years (CTS5) is a clinicopathological tool designed to estimate late distant recurrence (LDR) in hormone receptor-positive (HR+) breast cancer patients after 5 years of adjuvant endocrine therapy (ET). While intended as a prognostic algorithm, its predictive value for ET extension remains uncertain. Methods: The score was calculated in 4931 patients from four prospective randomized ABCSG trials (ABCSG-6, -6a, -8, and -16) with 250 LDR events. We assessed its prognostic power, calibration accuracy, and predictive value. Time to LDR was analyzed using Cox regression models. Results: In our cohorts, the CTS5 provided prognostic information whether used as a continuous or categorical score. In the ABCSG-8 cohort (n = 2054) and the combined ABCSG-6+8 cohort (n = 3308), a higher continuous score was significantly associated with increased LDR risk. The categorical CTS5 showed that high-risk patients had significantly higher LDR rates compared to low- or intermediate-risk patients. The score slightly overestimated LDR risk, regardless of predicted risk. Although no significant predictive value was found on the relative scale, an absolute LDR risk reduction of 23.4 % was found in patients with a high CTS5 of 5 when extended ET was administered additional five than two years. In patients with a CTS5 of 2, no benefit was found when ET was extended to 10 instead of 7 years. Conclusion: The CTS5 is a valid tool for LDR risk stratification in HR + breast cancer, but should be used cautiously for determining benefits from ET extension, as no significant predictive value was found.

The Clinical Treatment Score post-5 years (CTS5) is an easy-to-use tool estimating the late distant recurrence (LDR) risk in patients with hormone receptor-positive breast cancer after 5 years of endocrine therapy (ET). Apart from evaluating the prognostic value and calibration accuracy of CTS5, the aim of this study is to clarify if this score is able to identify patients at higher risk for LDR who will benefit from extended ET. Prognostic power, calibration, and predictive value of the CTS5 was tested in patients of the prospective ABCSG-06 and -0a6 trials (n = 1254 and 860 patients, respectively). Time to LDR was analyzed with Cox regression models. Higher rates of LDR in the years five to ten were observed in high- and intermediate-risk patients compared to low-risk patients (HR 4.02, 95

Purpose: Estrogen receptor (ER) expression predicts response to endocrine therapy and is a prognostic biomarker. However, no ER-associated biomarker is able to identify patients with particularly favorable outcome among ER+ tumors. We investigated the value of ESR1 amplification in predicting long-term outcome in tamoxifen-treated postmenopausal women with early breast cancer with and without nodal involvement. Patients and Methods: 394 patients with ER+ breast cancer (235 node-negative, 159 patients node- positive), who had received adjuvant tamoxifen for 5 years in the prospective randomized ABCSG-06 trial, and in whom FFPE tumor tissue was available, were included in this analysis. ER alpha immunoreactivity was evaluated using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis. Results: Focal ESR1 amplification was detected in 187 (47%) tumors, and was associated with a favorable outcome. After a median follow-up of 10 years, women with focal ESR1 amplification had a significantly longer distant recurrence-free survival (DRFS; adjusted HR 0.48; 95% CI 0.26-0.91; p=0.02) and breast cancer-specific survival (BCSS; adjusted HR 0.47; CI 0.27-0.80; p=0.01) compared to women without ESR1 amplification. The association between ESR1 amplification and improved DRFS and BCSS was only found in node-positive tumors, but not in nodal-negative tumors. ER alpha immunoreactivity, evaluated by Allred score, correlated significantly with focal ESR1 amplification (p< 0∙0001; Chi-squared test), but without prognostic significance. Conclusion: We suggest focal ESR1 amplification as predictor of improved long-term outcome in postmenopausal women with node-positive ER+ early breast cancer. Citation Format: Christian F. Singer, Frederik Holst, Stefan Steurer, Eike Burandt, Sigurd Lax, Raimund Jakesz, Margaretha Rudas, Herbert Stöger, Richard Greil, Guido Sauter, Martin Filipits, Ronald Simon, Michael Gnant. Focal ESR1 gene amplification is an independent prognostic marker in postmenopausal patients with endocrine-responsive early breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-15.

<p>PDF file - 34K, Supplementary Table S1. ROR cutoff values for risk groups defined by nodal status.</p>

Introduction: Oncoplastic techniques allow resection of larger tumors, permitting breast conservation in cases otherwise requiring mastectomy. We sought to prospectively compare quality of life (QoL) in patients under-going oncoplastic surgery as compared to conventional breast conservation (CBC) or mastectomy is lacking. Methods: Patients diagnosed with BIRADS IV-VI lesion were eligible if resection of >= 10% of the breast volume was planned. Patients were allowed to decide whether they wanted to undergo CBC or oncoplastic breast con-servation (OBC). Patients who underwent mastectomy and immediate breast reconstruction (IBR) were also included for comparison. The primary endpoint was breast self-esteem using the Breast Image Scale (BIS) at 12 months, secondary endpoints were perioperative morbidity and QoL using the BREAST-Q questionnaire. Results: From 2011 to 2016, 205 patients were included in the study. 116 patients (56.6%) received CBC, 46 (22.4%) OBC and 43 (21%) MIBR. Women in the OBC group were more likely to have tumors >= 2 cm than those in the CBC group (34.7% vs. 17.5%, respectively). Women who underwent MIBR were more likely to have tu-mors > 5 cm than those in the CBC and OBC groups (23% vs 1% and 10%, respectively). The BIS and BREAST-Q improved in each group after 12 months but did not differ significantly between groups at any time point. Surgical complications (seroma, bleeding, infection, necrosis) were numerically more likely in the OBC and MIBR groups. Conclusion: OBC and the MIBR allow for resection of larger tumors with a similar quality of life as CBC.

Abstract Purpose: Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer. Experimental Design: 394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERα expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indicating focal copy number alterations. Results: Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26–0.91; P = 0.02] and breast cancer–specific survival (adjusted HR 0.47; 95% CI, 0.27–0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 test), but was not prognostic by itself. Conclusions: Focal ESR1 amplification is an independent and powerful predictor for long-term distant recurrence-free and breast cancer–specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received tamoxifen for 5 years.

BackgroundAdjuvant aromatase inhibitors increase osteoporosis and fractures in patients with hormone receptor-positive breast cancer. We have previously reported outcomes of the ABCSG-18 (study 18 from the Austrian Breast & Colorectal Cancer Study Group) trial showing that adjuvant anti-receptor activator of nuclear factor-kappa B ligand denosumab treatment counteracts these adverse effects and may improve outcomes. We report here the final long-term outcomes.MethodsABCSG-18 is a prospective, double-blind, placebo-controlled, phase 3 trial in which 3425 postmenopausal patients with early hormone receptor-positive breast cancer receiving aromatase inhibitor therapy were randomly assigned in 58 trial centers to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months. The primary end point was the time to first clinical fracture after randomization. Secondary disease outcome-related end points were disease-free survival (DFS), bone metastasis-free survival (BMFS), and overall survival (OS).ResultsFor this final protocol-defined analysis, median follow-up is 8 years (interquartile range, 6 to 9.6 years). There were 309 versus 368 DFS events (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.97) in the denosumab versus the placebo group, respectively, resulting in an absolute 9-year DFS benefit of 3.5 percentage points (79.4 vs. 75.9%). Adjuvant denosumab improved BMFS by 2.5 percentage points (88.9 vs. 86.4%; hazard ratio, 0.81; 95% CI, 0.65 to 1.00) and OS by 1.0 percentage point (90.9 vs. 89.9%; hazard ratio, 0.80; 95% CI, 0.64 to 1.01). No new toxicities for this dose of adjuvant denosumab were observed.ConclusionsDFS, BMFS, and OS continued to show benefit in this final long-term analysis of ABCSG-18. There were no new toxicities. (Funded by Amgen; ClinicalTrials.gov number, NCT00556374.) In this long-term report of a prospective, double-blind, placebo-controlled, phase 3 trial of adjuvant aromatase inhibitor in postmenopausal patients with early hormone receptor-positive breast cancer, adjuvant denosumab therapy improved disease-free survival by 3.5 percentage points, bone metastasis-free survival by 2.5 percentage points, and overall survival by 1.0 percentage point at 9 years of follow-up.

BACKGROUND:For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear.METHODS:In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture.RESULTS:Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84).CONCLUSIONS:In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).

Background Preoperative chemotherapy containing anthracyclines and taxanes is well established in early-stage breast cancer. Previous studies have suggested that the chemotherapy sequence may matter but definitive evidence is missing. ABCSG trial 34 evaluated the activity of the MUC1 vaccine tecemotide when added to neoadjuvant treatment; the study provided the opportunity for the second randomisation to compare two different anthracycline/taxane sequences. Methods HER2-negative early-stage breast cancer patients were recruited to this randomised multicentre Phase 2 study. Patients in the chemotherapy cohort ( n = 311) were additionally randomised to a conventional or reversed sequence of epirubicin/cyclophosphamide and docetaxel. Residual cancer burden (RCB) with/without tecemotide was defined as primary study endpoint; RCB in the two chemotherapy groups was a key secondary endpoint. Results No significant differences in terms of RCB 0/I (40.1% vs. 37.2%; P = 0.61) or pathologic complete response (pCR) rates (24.3% vs. 25%, P = 0.89) were observed between conventional or reverse chemotherapy sequence. No new safety signals were reported, and upfront docetaxel did not result in decreased rates of treatment delay or discontinuation. Conclusion Upfront docetaxel did not improve chemotherapy activity or tolerability; these results suggest that upfront neoadjuvant treatment with anthracyclines remains a valid option.

PURPOSE:To investigate long-term results of patients with hormonal receptor-positive breast cancer treated with breast-conserving surgery (BCS) and consecutive endocrine therapy (ET) with or without whole breast irradiation (WBI). METHODS AND MATERIALS:Within the 8 A trial of the Austrian Breast and Colorectal Cancer Study Group, a total of 869 patients received ET after BCS which was randomly followed by WBI (n = 439, group 1) or observation (n = 430, group 2). WBI was applied up to a mean total dosage of 50 Gy (+/- 10 Gy boost) in conventional fractionation. RESULTS:After a median follow-up of 9.89 years, 10 in-breast recurrences (IBRs) were observed in group 1 and 31 in group 2, resulting in a 10-year local recurrence-free survival (LRFS) of 97.5% and 92.4%, respectively (p = 0.004). This translated into significantly higher rates for disease-free survival (DFS): 94.5% group 1 vs 88.4% group 2, p = 0.0156. For distant metastases-free survival (DMFS) and overall survival (OS), respective 10-year rates amounted 96.7% and 86.6% for group 1 versus 96.4% and 87.6%, for group 2 (ns). WBI (hazard ratio [HR]: 0.27, p < 0.01) and tumour grading (HR: 3.76, p = 0.03) were found as significant predictors for IBR in multiple cox regression analysis. CONCLUSIONS:After a median follow-up of 10 years, WBI resulted in a better local control and DFS compared with ET alone. The omission of WBI and tumour grading, respectively, were the only negative predictors for LRFS.

Abstract Background: Sentinel lymph node dissection identifies nodal positivity in early breast cancer. Trials like the ACOSOG Z0011 trial tried to show that the waiver of axillary dissection in nodal positive breast cancer (BC) has no effect on the oncologic outome, however real world data are rare and the role of adjuvant regional radiotherapy is still disputed in this respect. Objective: We initiated a multicenter observational registry to investigate omission of axillary lymph node dissection in nodal positive early BC. Design and Setting: The 18 sites participating in Austria and Switzerland included from 2014 to 2017 178 patients in this trail. Patients: Women with unilateral invasive lymph node positive BC with one or two sentinel lymph node makrometastases, who did not undergo axillary lymph node dissection were included. Results: We had a median follow up time of 3.1 years (range between 0.5 and 10.5 years), the median patient age is 63.6 years (range between 33 – 93 years). In 16.9% women had a G1 Grading, 53.1% had G2 tumor and 29.9% had a G3 tumor. Multifocality was seen in 18.1% of the patients. Luminal A tumors were seen in 16 (8.9%) and Luminal B in 82 (46.1%). Fourteen (7.8%) patients in this cohort had HER2 positive BC. In one (0.5%) local recurrence of the axilla occurred. Three (1.7%) of 178 patients died due to BC recurrence. Conclusion: Patients with macro metastasis in the sentinel lymph node, treated with breast conserving surgery and whole breast radiation did not have an increased risk of BC recurrence. Therefore the authors assume that axillary dissection in patients with early stage BC and macro metastasis is not necessary in this patient cohort. Citation Format: Strobl SA, Dubsky P, Exner R, Gnant M, Jakesz R, Tausch C, Wette V, Heck D, Luisser I, Bjelic-Radisic V, Schrenk P, Poyssl C, Mathis J, Fitzal F. ABCSG 33 - A multi center registry to evaluate the affect of macro metastasis in sentinel lymph node on survival [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 P3-03-24.

Background In postmenopausal women with hormone receptor-positive, early-stage breast cancer, treatment with adjuvant aromatase inhibitors is the standard of care, but it increases risk for osteoporosis and fractures. Results from the ABCSG-18 trial showed that use of denosumab as an adjuvant to aromatase inhibitor therapy significantly reduced clinical fractures. Disease-free survival outcomes from ABCSG-18 have not yet been reported. Methods Postmenopausal patients with early, hormone receptor-positive, non-metastatic adenocarcinoma of the breast, who had completed their initial adjuvant treatment pathway (surgery, radiotherapy, or chemotherapy, or a combination) and were receiving adjuvant aromatase inhibitors, were enrolled at 58 trial centres in Austria and Sweden into this prospective, double-blind, placebo-controlled, phase 3 trial. With permuted block randomisation (block sizes 2 and 4, stratified by previous aromatase inhibitor use, total lumbar spine bone mineral density score at baseline, and type of centre), patients were assigned (1: 1) to receive subcutaneous denosumab (60 mg) or matching placebo every 6 months during aromatase inhibitor therapy. The primary endpoint (previously reported) was the time to first clinical fracture after randomisation. The secondary endpoint reported here is disease-free survival (defined as time from randomisation to first evidence of local or distant metastasis, contralateral breast cancer, secondary carcinoma, or death from any cause) in the intention-to-treat population. This study is registered with EudraCT (number 2005-005275-15) and ClinicalTrials.gov (number NCT00556374), and is ongoing for long-term follow-up. Findings Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled and randomly assigned; 1711 to the denosumab group and 1709 to the placebo group (with five others withdrawing consent). After a median followup of 73 months (IQR 58-95), 240 (14.0%) patients in the denosumab and 287 (16.8%) in the placebo group had disease-free survival events. Disease-free survival was significantly improved in the denosumab group versus the placebo group (hazard ratio 0.82, 95% CI 0.69-0.98, Cox p=0.0260; descriptive analysis, without controlling for multiplicity). In the denosumab group, disease-free survival was 89.2% (95% CI 87.6-90.8) at 5 years and 80.6% (78.1-83.1) at 8 years of follow-up, compared with 87.3% (85.7-89.0) at 5 years and 77.5% (74.8-80.2) and 8 years in the placebo group. No independently adjudicated cases of osteonecrosis of the jaw or confirmed atypical femoral fractures were recorded. The total number of adverse events was similar in the denosumab group (1367 [including 521 serious] adverse events) and the placebo group (1339 [515 serious]). The most common serious adverse events were osteoarthritis (62 [3.6%] of 1709 in the denosumab group vs 58 [3.4%] of 1690 in the placebo group), meniscus injury (23 [1.3%] vs 24 [1.4%]), and cataract (16 [0.9%] vs 28 [1.7%]). One (< 0.1%) treatment-related death (due to pneumonia, septic kidney failure, and cardiac decompensation) occurred in the denosumab group. Interpretation Denosumab constitutes an effective and safe adjuvant treatment for patients with postmenopausal hormone receptor-positive early breast cancer receiving aromatase inhibitor therapy. Copyright (c) 2019 Elsevier Ltd. All rights reserved.

BACKGROUND:To evaluate whether uPA/PAI-1 protein in hormone receptor-positive (HR+) breast tumor can predict prognosis in early breast cancer (BC). METHODS:606 women with HR + BC who had ≥5 years of endocrine therapy and in whom tumor tissue was available were included in this analysis. Stromal uPA/PAI-1 protein expression was evaluated by immunohistochemistry and correlated with distant recurrence-free survival (DRFS) and overall survival (OS). RESULTS:Stromal uPA was detected in 292/538 tumors (54.3%) while 269/505 samples (53.3%) exhibited stromal PAI-1. Co-expression of both proteins was found in 163/437 (37.3%) samples. Stromal uPA/PAI-1 co-expression was not associated with tumor size, age, nodal status, grading, or receptor status. Tumor stroma with both uPA and PAI-1 protein expression were more likely to have a shorter DRFS (HR: 1.87; 95%CI 1.18-2.96; p = 0.007) and OS (HR: 1.29; 95%CI 0.93-1.80; p = 0.129) than women without uPA/PAI-1 co-expression. After a median follow-up of 10 years, women with uPA/PAI-1-positive tumors experienced a significantly shorter DRFS (86.5% vs 72.4%; p < 0.001) and OS (70.4% vs 58.9%; p = 0.020) compared to women with uPA/PAI-1 negative tumors. CONCLUSION:Stromal co-expression of uPA and PAI-1 in breast cancer predicts poor DRFS and OS in postmenopausal women with HR + early-stage BC who receive endocrine therapy.

Estrogen receptor (ER) determination as a means of predicting hormone dependency of human breast cancer is widely used and generally accepted. In particular, fluorescent bovine serum albumin conjugates which represent large, bulky ligands compared to E2, might not reach structure-associated receptors. With the exception of autoradiography and antireceptor antibody methods, the histochemical methods were criticized for claiming the localization of ER in tissue sections. Receptor specificity of ligand binding of biochemical and histochemical methods is demonstrated by competitive inhibition of the ligand-receptor interaction by unlabeled ligands with an affinity for the receptor similar to that of E2. Contamination of fluorescent ligands by noncovalently bound hormone has been implicated but not thoroughly investigated. Incubation of calf uterine cytosol with sepharose-bound conjugates resulted in a significant decrease of cytosolic ER content. Human breast cancer cell lines as model systems are well suited for testing and validation of fluorescent ligands devised for histochemical receptor localization.

500 Background: Adjuvant aromatase inhibitors (AI) are standard of care for postmenopausal women with hormone receptor positive (HR+) early stage breast cancer but cause osteoporosis and fractures. ABCSG-18 showed previously that adjuvant denosumab significantly reduces clinical fractures (primary endpoint, HR = 0.5, p < 0.0001, Lancet 2015). Here, we present the impact of adjuvant denosumab on disease-free survival. Patients and Methods: 3,425 postmenopausal patients with early HR+ BC receiving adjuvant AI were recruited in 58 trial centers into this prospective, double-blind, placebo-controlled, phase-III trial. Patients were randomized 1:1 to receive either denosumab 60mg s.c. (N = 1712) or placebo (N = 1713) q6 months during AI therapy. We here present results of ABCSG-18's secondary endpoint disease-free survival (DFS), including relevant subgroup and sensitivity analyses (accounting for cross-over either by censoring or by using a rank preserving structural failure time model). Results: After a median follow-up (FU) of 72 months, 287 events occurred in the placebo group, and 240 in the denosumab group. DFS was significantly improved in the denosumab arm (HR = 0.823, 95% CI 0.69-0.98, Cox p = 0.026*). In the denosumab group, DFS was 89.2% (95% CI 87.6-90.7) at 5 years and 80.6% (78.1-83.1) at 8 years of FU, compared to 87.3%, (85.7-89.0) at 5 years and 77.5% (74.8-80.2) at 8 years for patients who received placebo. Similar results were obtained from sensitivity analyses. No case of osteonecrosis of the jaw (ONJ) was recorded so far, despite proactive adjudication of potential cases by an independent expert panel. One potential atypical femur fracture was seen in the denosumab arm. Conclusion: Adjuvant denosumab improves disease-free survival of HR+ postmenopausal breast cancer patients receiving AI. Based on these results and the previously reported dramatic reduction of fractures, adjuvant denosumab 60mg s.c. q6 months should be offered to postmenopausal HR+ breast cancer patients receiving AI. * descriptive, without controlling for multiplicity. Clinical trial information: EudraCT #: 2005-005275-15.

Abstract 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 <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.