THE BREAST 19TH ST.GALLEN INTERNATIONAL BREAST CANCER CONFERENCE 2025 PRIMARY THERAPY OF PATIENTS WITH EARLY BREAST CANCER. EVIDENCE, CONTROVERSIES, CONSENSUS 12 - 15 MARCH 2025, VIENNA / AUSTRIA
Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia • San Diego • St. Louis Volume 79 February 2025 19th St. Gallen International Breast Cancer Conference 2025, 12–15 March 2025, Vienna/Austria Publication of this Abstract Supplement is sponsored by St.Gallen Oncology Conferences 80 Volume 80S February 2025
PRIMARY THERAPY OF EARLY BREAST CANCER Evidence, Controversies, Consensus 14th St.Gallen International Breast Cancer Conference Vienna, Austria, 18–21 March 2015 Conference Chairpersons Alan S. Coates, Melbourne, Australia Richard Gelber, Boston, USA Michel Gnant, Vienna, Austria Aron Goldhirsch, Lugano, Switzerland / Milan, Italy Martine Piccart, Brussels, Belgium Hans-Jo¨ rg Senn, St.Gallen, Switzerland Beat Thu¨ rlimann, St.Gallen, Switzerland 19th 2025, 12–15 March 2025, Vienna/Austria Individualizing therapy for patients with early-stage breast cancer: tailored local and systemic treatment Conference Chairs: Univ. Prof. Dr. Michael Gnant Medical University of Vienna / Austrian Breast&Colorectal Cancer Study Group / Austria Prof. Dr. Sibylle Loibl Goethe University Frankfurt/Main / German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg / Germany Prof. Dr. med. Beat Thürlimann Breast Centre, Kantonsspital St.Gallen and SwissBreastCare, Bethanienspital, Zurich / Switzerland Prof. Dr. Walter Weber University Hospital Basel / Switzerland Scientific Committee: Harold Burstein, Boston / United States of America David Cameron, Edinburgh / United Kingdom Giuseppe Curigliano, Milano / Italy Carsten Denkert, Marburg / Germany Michael Gnant, Vienna / Austria Sherene Loi, Melbourne / Australia Sibylle Loibl, Neu-Isenburg / Germany Philip Poortmans, Antwerp / Belgium Meredith Regan, Boston / United States of America Beat Thürlimann, St.Gallen / Switzerland Walter Weber, Basel / Switzerland Publication of this Abstract Supplement is sponsored by St.Gallen Oncology Conferences OF PATIENTS WITH EARLY BREAST CANCER
THE BREAST Editor-in-Chief Fatima Cardoso, ABC Global Alliance, Lisbon, Portugal Deputy Editor Karen Gelmon, BC Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada Specialty Editor S. Siesling, Netherlands A. Tagliafico, Genova, Italy S. Delaloge, Paris, France F. Penault-Llorca, Clermont-Ferrand, France J. Heil, Germany M.-J. Vrancken Peeters, Netherlands M. Oliveira Barcelona, Spain V. Müller, Germany P. Poortmans, Paris, France S. Di Cosimo, Milan, Italy G. Pravettoni, Milan, Italy H. Rugo, San Fransisco, USA Epidemiology: Imaging, Screening and Early Diagnosis: Prevention and Genetics: Pathology: Breast Surgery: Medical Oncology: Radiation Oncology: Translational Research: Psycho-oncology and Quality of Life: Social Media Editor: E. Elder, New South Wales, Australia S. Delaloge, Paris, France B. Thürlimann, St Gallen, Switzerland Australasian Society for Breast Disease (ASBD) Representative European Society for Medical Oncology (ESMO) Representative St. Gallen Oncology Conferences Representative Advisory Board B. Anderson MD, University of Washington, Seattle, Washington, USA B. Arun MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA H.A. Azim MD, American University of Beirut, Beirut, Lebanon G. de Bock PhD, University of Groningen, Groningen, Netherlands E. Brain MD, PhD, René Huguenin Hospital Saint-Cloud, St Cloud, France M. Brennan MD, PhD, The University of Sydney, Sydney, Australia J. Cortes MD, PhD Vall d’Hebron Institute of Oncology, Barcelona, Spain R. Dent MSc, MD, FRCP, Duke-NUS Medical School, Singapore, Singapore V. Diéras MD, Eugène Marquis Centre, Rennes, France L.E.M. Duijm MD, PhD, Canisius Wilhelmina Hospital, Nijmegen, Netherlands N. El Saghir MD, FACP, FASCO, American University of Beirut, Beirut, Lebanon J. Gligorov MD, PhD, Hospital Tenon, Paris, France S.-A. Im MD, PhD, Seoul National University, Gwanak-gu, South Korea G. Jerusalem MD, PhD, CHU de Liege - Hospital Sart Tilman, Liège, Belgium S.-B. Kim MD PhD, University of Ulsan College of Medicine, Songpa-gu, South Korea H. de Koning MD, PhD, Erasmus University Rotterdam, Rotterdam, Netherlands B. Linderholm MD, PhD, University of Gothenburg Sahlgrenska Academy, Göteborg, Sweden M. Marinovich PhD, MPH, The University of Sydney, Sydney, Australia R.A. Mukhtar MD, University of California San Francisco, San Francisco, California, USA S. Nakamura MD, Showa University Hospital, Shinagawa-Ku, Japan S. Ohno MD, The Cancer Institute Hospital Of JFCR, Koto-Ku, Japan M. Paesmans MSc, Jules Bordet Institute, Bruxelles, Belgium A. Partridge MD MPH, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, USA F.A. Peccatori MD, PhD, European Institute of Oncology, Milano, Italy I.-T. Rubio MD, PhD, University of Navarra, Pamplona, Spain V. Sacchini MD, Memorial Sloan Kettering Cancer Center, New York, New York, USA K. Sandelin MD, PhD, FACS, FRCS, Karolinska Institute, Stockholm, Sweden F. Sardanelli MD, University of Milan, Milano, Italy E. Senkus-Konefka, Gdansk, Poland V. Speirs PhD, FRCPath, FHEA, University of Aberdeen, Aberdeen, UK B. Xu MD, China Academy of Chinese Medical Sciences, Beijing, China S. Zackrisson MD, PhD, Lund University, Lund, Sweden J. Zgajnar MD, PhD, Institute of Oncology Ljubljana, Ljubljana, Slovenia
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Primary Therapy of Patients with Early Breast Cancer. Evidence, Controversies, Consensus 20th St.Gallen International Breast Cancer Conference 2027 17 – 20 March 2027, Vienna / Austria Save the Date 2027 www.sg-bcc.org
THE BREAST Poster Abstracts Adjuvant Systemic Therapy S1 Targeted Therapy S8 Biology/Pathology/Basic Research S13 Biomarkers S24 Diagnostics/Imaging/Artificial Intelligence S33 Epidemiology/Prevention/Diagnosis S48 Locally Advanced Disease S58 Radiotherapy/IORT S63 Neoadjuvant (Pre-operative) Therapy S72 Health Politics/Guidelines S89 Predictive and Prognostic Factors S95 Surgery/Sentinels/DCIS S108 Survivorship Issues S156 Supportive Care S165 Trials in Progress S168 Other S173 Author Index S189 VOLUME 80S FEBRUARY 2025
vii Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer I. Meattini, I. Desideri, V. Scotti, G. Simontacchi and L. Livi 1 Therapeutic Drug Monitoring of endoxifen as an alternative for CYP2D6 genotyping in individualizing tamoxifen therapy A.H.M. de Vries Schultink, A.D.R. Huitema and J.H. Beijnen 38 Guide for Authors Submission to The Breast proceeds totally online via the Elsevier Editorial System page of this journal at http://ees.elsevier.com/thebreast/. Authors will be guided through the creation and uploading of the various files. Once the uploading is done, the system automatically generates an electronic (PDF) proof, which is then used for reviewing. All correspondence, including the Editor’s decision and request for revisions, will be by e-mail. Authors may send queries concerning the submission process, manuscript status, or journal procedures to the editorial office at thebreast@elsevier.com Indexed/abstracted in: Index Medicus, MEDLINE, ABI/Inform, Current Awareness in Biological Sciences, Current Contents/Clinical Medicine, EMBASE, Excerpta Medica National Library of Medicine (MEDLARS and MEDLINE), Research Alert, SCISEARCH, Science Citation Index Expanded, Scopus Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia • San Diego • St Louis Available online at www.sciencedirect.com ScienceDirect YBRST_v42_iC_FM.indb iv 10/17/2018 12:42:4 The Breast proceeds totally online via the Elsevier Editorial System page of this journal at https://www.editorialmanager.com/thebreast.
Poster Abstracts Adjuvant Systemic Therapy P001 Prognostic variables for risk of recurrence in patients (pts) with HR+/HER2–early breast cancer (EBC) using data from the NATALEE trial: a machine learning (ML) model–based analysis P.A. Fasching1, C.H. Barrios2, E. Lim3, S.L. Graff4, S. Chia5, J.-S. Frenel6, S.-A. Im7, C.-S. Huang8, A. Ring9, Z. Nowecki10, Q. Liu11,M. Akdere12, J.P. Zarate13, H. Hu13, K. Pantoja14, J.A. O’Shaughnessy15. 1University Hospital Erlangen Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany; 2Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil; 3Garvan Institute of Medical Research & Faculty of Medicine, St. Vincent’s Clinical School, University of New South Wales, Sydney, New South Wales, Australia; 4Brown University Health Cancer Institute, Legorreta Cancer Center at Brown University, Providence, United States; 5British Columbia Cancer Agency, Vancouver, BC, Canada; 6Institut de Cancérologie de l’Ouest, GINECO, GINEGEPS, Centre René Gauducheau, Saint-Herblain, France; 7Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Republic of; 8National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan; 9Royal Marsden Hospital NHS Foundation Trust, Surrey, United Kingdom; 10The Maria Sklodowska Curie Centre, Warsaw, Poland; 11Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; 12Novartis Pharma AG, Basel, Switzerland; 13Novartis Pharmaceuticals Corporation, East Hanover, United States; 14Novartis Pharmaceuticals Corporation, Cambridge, United States; 15Texas Oncology, Baylor University Medical Center, Sarah Cannon Research Institute, Dallas, United States Goals: The phase 3 NATALEE trial, conducted in a broad population of pts with stage II/III HR+/HER2–EBC, demonstrated a statistically significant invasive disease–free survival (iDFS) benefit with ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) vs NSAI alone; this benefit was maintained even after all pts were off RIB treatment (tx) (HR, 0.715). Identifying prognostic factors and obtaining insights into how they affect recurrence risk is critical for making tx decisions in HR+/HER2–EBC. Methods: NATALEE enrolled 5101 pts with stage IIA (node negative [N0] with additional risk factors or N1), stage IIB, or stage III disease per AJCC (8th edition). This analysis focused on 3 distinct time-toevent endpoints: STEEP-defined iDFS and distant disease–free survival (DDFS), as well as time to recurrence-related events, defined as time to recurrence (TTR). For each respective endpoint, an ML model (conditional inference random forest model) was used to rank the variables of importance from a set of 79 baseline covariates, including pt baseline demographic and disease characteristics and prior tx history. Model performance was assessed in test sets using concordance index (C-index). In addition, the model was employed to derive a predicted recurrence score based on all baseline covariates. The relationships between the predicted recurrence risk score and the clinical outcome endpoint, and between the recurrence score and each covariate, were investigated. Results: All 5101 pts enrolled in NATALEE were included in this analysis; 2526 received RIB + NSAI and 2441 received NSAI only. The recurrence risk score showed a strong correlation with each respective recurrence outcome endpoint. The 6 most important prognostic variables for all 3 outcome endpoints, iDFS (test set Cindex, 0.644), DDFS (C-index, 0.647), and TTR (C-index, 0.670), are listed in Table 1. An iDFS, DDFS, and TTR benefit with RIB + NSAI vs NSAI alone was observed both for pts with a recurrence risk score above and at or below the median (Table 2). Conclusions: Variables such as stage, nodal status, and prior neoadjuvant CTwere identified byour ML approach as critical prognostic factors. Further analyses should focus on validating these findings and their usability in predicting the recurrence risk. In this analysis using the NATALEE trial population, the efficacy benefit with RIB + NSAI was consistent regardless of the recurrence risk predicted by ML. Table 1. The Most Important Prognostic Variables for Predicting Recurrence in Pts With HR+/HER2–EBC. iDFS DDFS TTR Prognostic variable in orderof importance Anatomic stagea Anatomic stagea Anatomic stagea Estrogen receptor scoreb PriorNACT Nodal statusc Nodal statusc Nodal statusc PriorNACT PriorNACT Age at baseline Estrogen receptor scoreb Tumor statusd, e Tumor statusd, e Local HER2 IHC scoref Progesterone receptor scoreb Estrogen receptr scoreb Histopathological grade DDFS, distant disease–free survival; EBC, early breast cancer; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; iDFS, invasive disease–free survival; IHC, immunohistochemistry; NACT, neoadjuvant chemotherapy; TNM, tumor, node, metastasis; TTR, time to recurrence. aIA, IB, IIA, IIB, IIIA, IIIB, IIIC. bNo cutoff was used for hormone receptor scoring. cNx, N0, N1, N1mi, N2, N3. dTx, Tis, T0, T1, T2, T3, T4. eAccording to TNM staging. fScoring based on 0–3+ IHC scores determined prior to surgery. Table 2. Efficacy of RIB + NSAI vs NSAI Alone for Pts With Recurrence Score ≤Median and > Median. iDFS (median, −0.207) DDFS (median, −0.207) TTR (median, −0.216) Recurrence risk≤ median, HR (95% CI) 0.77 (0.58−1.03) 0.63 (0.46−0.84) 0.68 (0.48−0.96) Recurrence risk > median, HR (95% CI) 0.75 (0.62−0.92) 0.83 (0.67−1.02) 0.75 (0.60−0.93) DDFS, distant disease-free survival; HR, hazard ratio; iDFS, invasive disease– free survival; NSAI, nonsteroidal aromatase inhibitor; RIB, ribociclib; TTR, time to recurrence. The Breast 80S (2025) S1–S188 Contents lists available at ScienceDirect The Breast journal homepage: www.elsevier.com/brst S0960 9776/ © 2025 Elsevier Ltd. All rights reserved.
The Breast 80S (2025) 103895 https://doi.org/10.1016/j.breast.2025.103895 P002 Genomic And Transcriptomic Profiling of Primary Tumors From Patients with HR+, HER2-, Node-positive, High-risk Early Breast Cancer (EBC) in the monarchE Trial C.S. Rubenstein1,N. Turner2, J.S. Reis-Filho3, M.P. Goetz4, C. Desmedt5, S. Chandarlapaty6,H. Sasano7, C.L. Arteaga8, S. Loi9, S.L. Graff10,D. Liu1, V. Rodrik-Outmezguine1, A. Sireci1, H.Won1, L.M. Litchfield1, M.Munoz1, S. Johnston2. 1Eli Lilly and Company, Indianapolis, IN, United States; 2Department of Medicine-Breast Unit, Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom; 3Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States; 4Department of Oncology, Mayo Clinic, Rochester, Rochester, MN, United States; 5Department of Oncology, KU Leuven, Laboratory for Translational Breast Cancer Research, Leuven, Belgium; 6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, United States; 7Department of Pathology, Tohoku University Hospital, Sendai, Japan; 8UT Southwestern Simmons Comprehensive Cancer Center, Dallas, United States; 9Division of Cancer Research, Peter MacCallum Cancer Center, Melbourne, Australia; 10Lifespan Cancer Institute, Legorreta Cancer Center at Brown University, Providence, United States Goals: Two years of adjuvant abemaciclib+endocrine therapy (ET) resulted in significantly and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high-risk EBC in the monarchE trial (NCT03155997). To report comprehensive molecular profiling of archived primary tumor tissue and association with clinical outcomes in patients from the monarchE trial. Methods: A proportionally stratified random sampling case-cohort design was used to include all pts with an IDFS event. Abemaciclib+ET arm tumor samples were matched 1:1 with ET arm samples. Baseline primary tumor underwent exome-capture RNA sequencing (RNAseq; n = 1324) and paired tumor-normal whole-exome sequencing ([WES]; n = 1234). Expression-based intrinsic subtypes (luminal A/ luminal B [LumA/LumB], HER2-enriched [HER2E], basal- and normallike) were characterized. The 21-gene expression signature score (Oncotype DX test) was inferred from RNAseq; samples were categorized in low (0–25) and high (26–100) risk groups. WES genomic events including oncogenic and hotspot mutations and copy number events of incidence >9% were selected. Results: A total of 1190 tumors (abemaciclib+ET n = 605; ET alone n = 585) yielded adequate RNAseq results. Subtypes distribution was consistent across treatment arms. Low tumor purity limited normallike subtype assessment. Abemaciclib IDFS benefit was consistent across all subtypes (HRs ranging from 0.49 to 0.75). Risk of recurrence was lowest for LumA and highest for HER2E and basal-like (4-year IDFS rates in ET arm: 81.4%, 42.5% and 46.7%, respectively). Inferred 21-gene expression signature score showed similar benefits from abemaciclib in both lower (HR:0.50, 95%CI:0.33–1.1) and high-risk groups (HR:0.73, 95%CI:0.57–0.92). A total of 1173 tumors yielded adequate WES results (abemaciclib+ET [n = 580]; ET alone [n = 593]). Abemaciclib benefit was consistent across frequently altered genes (including PIK3CA and p53 mutations, and CCND1 amplification) with the exception of MYC amplified tumors (HR:1.3, 95%CI:0.77– 2.20). Conclusions: Adjuvant abemaciclib+ET maintained IDFS benefit vs ET alone across molecular subtypes per RNAseq. Benefit was consistent across most altered genes assessed by WES, except for MYC amplification subset. Additional research is needed to confirm these findings. The Breast 80S (2025) 103896 https://doi.org/10.1016/j.breast.2025.103896 P003 Risk of Recurrence by Nodal Status and High-Risk Features in Patients with HR+, HER2-, Early Breast Cancer: An Analysis of RealworldData B. Grimes1, S.M Tolaney2, S. Sammons2, J. Cortes3, A.MLiepa1, T. Sugihara4,Z. LinCui1, W. Gathirua-Mwangi1,A. Shahir1,M.Monaco1, P. Neven5, S. Johnston6. 1Eli Lilly and Company, Indianapolis, IN, United States; 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States; 3Department of Medicine, Institute International Breast Cancer Center, Pangaea Oncology, Quironsalud Group, Barcelona, Spain;, Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Madrid, Spain; 4Syneos Health, North Carolina, United States; 5University Hospitals Leuven, Louvain, Belgium; 6The Royal Marsden NHS Foundation Trust, London, United Kingdom Goals: Tumor involvement of axillary lymph nodes (ALN) is a significant prognostic marker for recurrence in HR+, HER2- early breast cancer (EBC). Most patients (pts) with node-positive EBC have 1–3 ALN (N1) disease, but outcomes for N1 disease vary. The monarchE trial selected pts with high-risk features of positive nodal status, including 4–9 ALN (N2) or ≥10 ALN (N3), and N1 disease with tumor size > = 5 cm or grade 3. This study evaluates the risk of recurrence in pts with N1 disease with and without high-risk features, as well as outcomes for pts with node-negative (N0), N2, and N3 disease. Methods: A nationwide Flatiron Health electronic health record derived de-identified database was used. Eligible pts had stage I-III, HR+, HER2- disease, underwent surgery for primary breast tumor, and initiated adjuvant endocrine therapy (ET) from Jan 2011–March 2020. Pts with N1 disease and high-risk features were assigned to the high-risk group (N1-HRG), while those with N1 disease not meeting monarchE criteria were assigned to the non-high-risk group (N1NHRG). Invasive disease-free survival (IDFS) was defined as time from adjuvant ET initiation to recurrence or death using Kaplan-Meier method. Hazard ratios (HR) for HRGs vs NHRGs vs N0 were estimated using Cox proportional hazards models. Results: A total of 4658 pts were eligible, with N1-HRG (286), N2 (161), N3 (99), and NHRG (3999; N1-NHRG [548], N0 [3293]). Median follow-up was 43.5 months for N1-HRG+N2+N3 and 42.2 months for NHRG. For N1-HRG, pts had stage II (67%), grade 3 (82%), and tumor size≥5 cm (25%). The 5-year (y) IDFS rates were 74% for N1-HRG, 89% for N1-NHRG, and 93% for N0. Recurrence risk for N1-HRG was >2fold higher than N1-NHRG and N0, with adjusted HR (95%CI) of 2.18 (1.45, 3.29; nominal p = 0.0002) and 2.97 (2.19, 4.02; nominal p < 0.0001), respectively. The 5y IDFS rates were 66% for N2, 65% for N3, and 71% for N1-HRG+N2+N3. Compared to NHRG, the HR (95% CI) for N2, N3, and N1-HRG+N2+N3 were 3.68 (2.63, 5.15), 4.03 (2.75, 5.91), and 3.25 (2.62, 4.03) respectively. Conclusions: These real-world data demonstrate that pts with N1 EBC and high-risk features have a recurrence risk of 26% at 5y which is nearly as high as recurrence risk in pts with N2/N3 disease. In contrast, pts with N1 EBC without high-risk features had 11% recurrence risk at 5y, similar to N0 disease. Pts who met monarchE criteria (N1-HRG, N2, N3 EBC) had a 5 y risk of recurrence of 29%, supporting the use of adjuvant abemaciclib+ET in these pts with high-risk EBC. The Breast 80S (2025) 103897 https://doi.org/10.1016/j.breast.2025.103897 Poster Abstracts / The Breast 80S (2025) S1–S188 S2
P004 Clinical Characteristics and Treatment Persistence in US Patients with HR+/HER2-, Node Positive Early Breast Cancer Treated with Abemaciclib: Real-World Study from First Year After Approval K. Hudson1, W. Gathirua-Mwangi2, Z.L. Cui2,M. Richey3, B. Grimes2, J.Wang3, A.MLiepa2, E. Brechtelsbauer2, R. Volodarsky2, K. Moreira2, H. Soliman4. 1Texas Oncology, Austin, TX, United States; 2Eli Lilly and Company, Indianapolis, IN, United States; 3Flatiron Health, New York City, NY, United States; 4Moffitt Cancer Center and Research Institute, Tampa, FL, United States Goals: Abemaciclib in combination with endocrine therapy (ET) is approved for adjuvant treatment of adult patients with HR+/HER2-, node-positive, early breast cancer (EBC) at high risk of recurrence. This retrospective study describes clinical characteristics and treatment persistence in patients with HR+/HER2-, node positive EBC initiating abemaciclib. Methods: Data were accessed from Flatiron Health electronic database. Adult patients with node positive, stage I–III EBC initiating abemaciclib Oct 2021 (FDA approval) to Nov 2022 at 150mg twice daily (BID) were analyzed. Persistence rate was defined as the percentage of patients remaining on abemaciclib at 3 months allowing for ≤60-day medication gap. Results: A cohort of 354 patients with a median follow-up time from abemaciclib initiation of 8.8 months were selected. The median age was 56 years 25.4% were ≥65 years old, 12.7% were Black, 4.0% were Asian, and most patients (80.8%) received care in a community setting. Over half (55.4%) patients were postmenopausal; 57.9% had an ECOG performance status (PS) 0, while 25.1% had ECOG PS 1. Approximately 33.9% had ≥1 comorbidity and 12.1% had ≥2 comorbidities with diabetes (14.1%) being the most frequent. Most patients had stage II (41.8%) or III (38.4%) disease, nodal status N1 (45.2%) or N2 (35.3%), and tumor grade 2 (52.3%). Abemaciclib was initiated at a median of 11.1 months after EBC diagnosis. Prior to abemaciclib initiation, most patients received radiotherapy (96.3%) and chemotherapy (83.1%), with 46.3% receiving neoadjuvant chemotherapy. Most patients (74.0%) initiated ET 1.6 months prior to abemaciclib initiation. The median time to abemaciclib initiation from breast surgery was 6.7 months. The most frequent regimen was abemaciclib + aromatase inhibitors (91.0%). At 3 months, 81.6% of patients were persistent; 5.6% resumed abemaciclib after >60-day interruption and 11.3% discontinued due to adverse events. Additional information on dose modifications will be presented. Conclusions: In this real-world study of utilization of abemaciclib in the first year after approval for EBC, an older, less fit, and more racially diverse population than participated in the monarchE trial, as well as a higher proportion of patients with lower nodal status was observed. The high three-month persistence rate suggests abemaciclib for EBC is well-tolerated in routine clinical practice. The Breast 80S (2025) 103898 https://doi.org/10.1016/j.breast.2025.103898 P005 Impact of Dose Reductions on Efficacy of Adjuvant Abemaciclib for Patients with High Risk Early Breast Cancer: Analyses from the monarchE Study V.Andre1, J.O’Shaughnessy2, I.Cicin3, L. Testa4, S. Tolaney5, J.Huober6, V. Guarneri7, S. Johnston8,M.Martin9, P. Rastogi10, N. Harbeck11, H. Rugo12, R.Wei1, A. Shahir13,M. Goetz14. 1Eli Lilly and Company, Indianapolis, IN, United States; 2Oncology, Baylor University Medical Center, Texas Oncology; Sarah Cannon Research Institute, US Oncology Network, Dallas, United States; 3Trakya University Faculty of Medicine, Edirne, Turkey, Edrine, Turkey; 4Instituto D’Or de Pesquisa e Ensino (IDOR), Sao Paulo, Brazil, Rio de Janeiro, Brazil; 5Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, United States; 6Cantonal Hospital St. Gallen, Breast Centre St. Gallen, Switzerland and University of Ulm, Dept of Gynecology, Germany, St. Gallen, Switzerland; 7Department of Surgery, Oncology and Gastroenterology, Padova, Italy; 8Royal Marsden NHS Foundation Trust, London, United Kingdom, London, United Kingdom; 9Hospital General Universitario Gregorio Marañon, Universidad Complutense, CIBERONC, GEICAM, Madrid, Spain, Madrid, Spain; 10University of Pittsburgh/UPMC, NSABP Foundation, Pittsburgh, PA, USA, Pittsburgh, United States; 11Breast Centre, Department of Gynaecology and Obstetrics, Comprehensive Cancer Centre München, LMU University Hospital, Munich, Germany, Munich, Germany; 12University of California San Francisco Hellen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA, San Francisco, United States; 13Loxo@Lilly, Indianapolis, IN, United States; 14Department of Oncology, Mayo Clinic, Rochester, MN, USA, Minnesota, United States Goals: Abemaciclib is approved as adjuvant therapy for HR+, HER2-, high risk EBC based on clinically significant improvements in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), which were maintained and deepened after the 2-year treatment period was completed. In monarchE, 44% of patients required dose reductions of abemaciclib to proactively manage adverse events. In abemaciclib MBC trials, similar rates of dose reductions did not compromise PFS (Rugo, 2021). Here we present the exploratoryanalyses to investigate the impact of dose reductions on efficacy in monarchE. Methods: In monarchE, up to 2 abemaciclib dose reductions were permitted prior to discontinuation. Pts treated with abemaciclib were classified into 3 equal-sized subgroups according to their abemaciclib relative dose intensity (RDI), and IDFS rates were estimated within each subgroup. A time-dependent Cox proportional hazard (PH) model (Therneau, 2000) was also implemented to assess the impact of dose levels over time on IDFS. Results: Among the 2791 pts treated with abemaciclib, 832 (30%) had one and 389 (14%) had two dose reductions. Patients≥65 years old, or thosewith ≥4 pre-existing co-morbidities were more likely to have dose reductions. Across the 3 RDI groups (≤66% vs 66%-93% vs≥93%), 4-year IDFS rates were generally consistent (87.1% vs 86.4% vs 83.7% from the lowest RDI group to the highest). According to the timedependent model, the effect of abemaciclib is similar when staying at the full 150mg dose compared to being dose reduced to either 100mg or 50mg (HR = 0.905; 95% CI = 0.727, 1.125). Conclusions: Consistent with observations in the metastatic setting, the efficacy of adjuvant abemaciclib in monarchE was not compromised by dose reductions. Therefore, dose reductions should be considered as a safe and effective way to manage toxicity and retain patients on treatment, in order to maintain benefit from adjuvant abemaciclib in combination with endocrine therapy. Originally presented at European Society for Medical Oncology 48th Congress - ESMO 2023, and includes data from Goetz M et al. NPJ Breast Cancer; https://doi.org/10.1038/s41523-024-00639-1. The Breast 80S (2025) 103899 https://doi.org/10.1016/j.breast.2025.103899 P006 Retrospective Analysis of Adjuvant Capecitabine for TripleNegative Breast Cancer After Preoperative Chemotherapy G. Lendinez-Sanchez1, A. Godoy-Ortiz1, A.M. Lopez-Pascual1, N. Ribelles1, E. Villar Chamorro1, B.I. Pajares Hachero1, T. Diaz Redondo1, J. Pascual1, M.E. Domínguez-Recio1, F. Carabantes Ocon1, M.J. Bermejo1, M. Zalabardo-Aguilar1, A. Rueda-Dominguez1,2, E. Alba-Conejo1,2, A. Sanchez-Muñoz1,2. 1Medical Oncology, Intercenter Unit. Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain, Málaga, Spain; 2Facultyof Medicine, University of Malaga (UMA), Málaga, Spain Goals: To evaluate real-world outcomes in three cohorts of patients with early triple-negative breast cancer (TNBC) treated with 19th St.Gallen International Breast Cancer Conference / The Breast 80S (2025) S1–S188 S3
neoadjuvant chemotherapy (NAC): Cohort 1 (C1): patients who achieved a pathological complete response (pCR); Cohort 2 (C2): patients who did not achieve a pCR and did not receive adjuvant capecitabine; Cohort 3 (C3): patients who did not achieve a pCR and received adjuvant capecitabine. Methods: We performed a retrospective analysis of 165 patients diagnosed of TNBC treated with NAC consisting of anthracyclines and cyclophosphamide followed by taxanes, with or without carboplatin. Patients who achieved a pCR did not receive adjuvant treatment. From January 2008 to June 2015 patients who did not reach a pCR they did not receive systemic therapy. Since July 2015 based on results reported by CREATEx trial, patients who did not reach a pCR received adjuvant capecitabine. Disease-free survival (DFS) and overall survival (OS) curves were estimated for each cohort. Multivariate cox regression analysis of prognostic variables for DFS and OS were realized. Results: Median follow-up was of 61 months (8–191). Patient distribution, recurrence and exitus stratified by cohort are listed in table1. Total population C1 C2 C3 165 70 55 40 No recurrence 114 63 28 23 Recurrence 51 7 27 17 Locorregional 14 1 8 5 Distant 37 6 19 12 Exitus 44 7 23 14 Median DFS or OS was not reached. Patients in C1 had a significantly higher DFS and higher OS compared with patients in C2 and C3. [Log-rank test for DFS: C1 vs C2 p = 0.000007; C1 vs C3 p = 0.000016; C2 vs C3 p = 0.665. Log-rank test for OS: C1 vs C2 p = 0.000029, C1 vs C3 p = 0.000047; C2 vs C3 p = 0.614]. Multivariate analysis revealed that failure to achieve a pCR was associated with a significantly higher risk of event in terms of both DFS and OS. While patients with N0 lymph nodes prior to NAC had a lower risk of dying. Multivariate cox regression analysis are shown in table 2 and 3. Table 2. Multivariate Cox Regression Analysis of Clinicopathological Variables for DiseaseFree Survival. Variable Hazard ratio (95% CI) P value ≥40y vs < 40y 1.62 (0.623–4.128) 0.324 Postmenopause vs premenopause 1.09 (0.585–2.046) 0.779 ≤5cmvs > 5cm 0.733 (0.404–1.33) 0.306 N0vsN+ 0.579 (0.327–1.023) 0.06 Ki67≤50%vs >50% 1.112 (0.621–1.991) 0.721 Non pCR vs pCR 5.148 (2.172–12.205) 0.0002 Adjuvant capecitabine 1.02 (0.541–1.923) 0.951 Table 3. Multivariate Cox Regression Analysis of Clinicopathological Variables for Overall Survival. Variable Hazard ratio (95% CI) P value ≥40y vs < 40y 1.39 (0.488–3.961) 0.538 Postmenopause vs premenopause 1.235 (0.619–2.464) 0.550 ≤5cmvs > 5cm 0.657 (0.344–1.254) 0.203 N0vsN+ 0.482 (0.257–0.904) 0.023 Ki67≤50%vs >50% 0.981 (0.517–1.862) 0.981 Non pCR vs pCR 4.076 (1.692–9.821) 0.002 Adjuvant capecitabine 1.006 (0.498–2.034) 0.987 Conclusions: Patients with pCR had better outcomes than those without pCR. Among patients without pCR, adjuvant capecitabine did not improve DFS or OS compared to those who did not receive adjuvant therapy. Adjuvant capecitabine may not benefit all earlystage invasive TNBC patients with residual disease after NAC in realworld settings. The Breast 80S (2025) 103900 https://doi.org/10.1016/j.breast.2025.103900 P007 Optimal Perioperative Treatment for HER2-Positive Breast Cancer H. Matsuzaki1, H. Sakata1, T. Aoyagi1,M. Namura1, T. Tamanuki1, M. Iwai1, N. Sasahara2, S. Mizuuchi2. 1Department of Breast Surgery, Funabashi Municipal Medical Center, Funabashi City, Japan; 2Nursing Department, Funabashi Municipal Medical Center, Funabashi City, Japan Goals: Anthracycline and taxane regimens combined with trastuzumab (TZB) and pertuzumab (PER) are standard for stage III and nodepositive HER2-positive breast cancer. However, variability exists in treatment strategies, including drug selection and neoadjuvant chemotherapy (NAC) indications, for stage I and node-negative stage II (T2N0) cases. This study aims to determine optimal treatments for these stages. Methods: We retrospectively analyzed 372 HER2-positive breast cancer patients who underwent surgery at our institution (April 1994–December 2022). Analyses included: 1. Treatment regimens and 5-year recurrence-free survival (RFS) by stage. 2. Tumor size, TZB use, and 5-year RFS in stage I. 3. Differences in RFS between T2N0 and T1N1 in stage IIA, and PER addition in T2N0 cases. Results: 1. By stage:. • Stage I (n = 116): RFS was 78.6% for untreated cases, 90.0% for TZBonly and chemotherapy-only cases, and no recurrences for chemotherapy + TZB. • Stage II (n = 190): RFS was 60% for untreated cases, 63.7% for chemotherapy-only, 79.4% for TZB-only, and 89.8% for chemotherapy + TZB. • Stage III (n = 65): RFS was 57.0% even with chemotherapy + TZB. 2. Stage I (116 cases) - Tumor size and RFS: • T1mi, 100%; T1a, 78.6%; T1b, 94.7%; T1c, 95.2%. • Among T1mi and T1a cases (n = 32), five recurrences (15.6%) occurred, all without TZB. T1b (n = 19) and T1c (n = 65) recurrences were 1 case (5.3%) and 3 cases (4.6%), respectively, all in non-TZB cases. • Among T1c patients receiving TZB (n = 50): regimens included anthracycline + taxane or TC(docetaxel,cyclophosphamide) (n = 25), either anthracycline or taxane (n = 17), oral 5-FU (n = 1), TZB monotherapy (n = 7), and PER addition (n = 6). • Overall RFS: 84.6% without TZB (n = 39) vs. 98.6% with TZB (n=77). 3. Stage IIA (129 cases) - RFS differences: • T2N0 (n = 108): RFS 87.5%. • T1N1 (n = 21): RFS 68.8%. • T2N0 cases receiving chemotherapy + TZB (n = 59): RFS 97.1% without PER (n = 38) vs. 100% with PER (n = 21). 3 recurrences occurred in non-PER-treated cases (7.9%), while no recurrences were observed in PER-treated cases. Conclusions: In stage I, chemotherapy + TZB prevented recurrence, suggesting limited NAC necessity. TZB is essential even for T1a or smaller tumors due to observed recurrences without TZB. Chemotherapy + TZB is the standard for T1b and T1c, with PER addition unnecessary. Anthracycline omission may be feasible based Poster Abstracts / The Breast 80S (2025) S1–S188 S4
on APT trial results. In stage IIA, PER addition is critical for T2N0 cases, and NAC-guided treatment may contribute to improved prognosis. The Breast 80S (2025) 103901 https://doi.org/10.1016/j.breast.2025.103901 P008 Prognostic Utility of ctDNA Detection in The monarchE Trial of Adjuvant Abemaciclib Plus Endocrine therapy (ET) in HR+, HER2-, Node-positive, High-risk Early Breast Cancer (EBC) S. Loi1, S. Johnston2, C. Arteaga3, S. Graff4, S. Chandarlapaty5, M. Goetz6, C. Desmedt7, H. Sasano8, D. Liu9, V. Rodrik-Outmezguine9, A. Sireci9, C. Sandoval9,H.Won8, L. Litchfield9,N. Turner2. 1Division of Cancer Research, Peter MacCallum Cancer Center, Melbourne, Australia , Melbourne, Australia; 2Department of Medicine-Breast Unit, Royal Marsden Hospital and Institute of Cancer Research, London, UK, London, United Kingdom; 3UT Southwestern Simmons Comprehensive Cancer Center, Dallas, Texas, USA, Dallas, United States; 4Lifespan Cancer Institute, Legorreta Cancer Center at Brown University, Providence, RI, USA, Providence, United States; 5Human Oncology and Pathogenesis Program, Memorial Sloan Kettering, New York, NY, United States; 6Department of Oncology, Mayo Clinic, Rochester, New York, USA, Rochester, United States; 7Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium, Leuven, Belgium; 8Department of Pathology, Tohoku University Hospital, Sendai, Japan, Sendai, Japan; 9Eli Lilly and Company, Indianapolis, United States Goals: In monarchE (NCT03155997), 2 years of adjuvant abemaciclib (abema)+ET resulted in sustained improvement in invasive diseasefree survival (IDFS; HR = 0.680, 7.6% absolute benefit at 5 years) in patients (pts) with HR+, HER2-, node-positive, high-risk EBC. Here, we investigate the prognostic value of ctDNA detection and dynamics in pts from monarchE. Methods: Samples were analyzed from a selected pt subset (n = 1397; abema+ET, n = 685; ET, n = 712), enriched for overall IDFS events vs total monarchE study population (IDFS event rate: 31% [433/1397] vs 18% [992/5637]). Pts had blood collected pre-study treatment (tx) (baseline) and at 3, 6, or 24 months. ctDNA detection was performed using tumor informed Signatera ctDNA assay and whole exome sequencing (WES) of matched primary tumor and normal required for assay design was performed. Results: Of 1397 pts, 65% (n = 910) had sufficient plasma samples and WES performed, and all 910 had successful ctDNA assay testing. Among these 910 pts, the IDFS event rate was 27% (abema+ET, 23% [101/438]; ET alone, 31% [146/472]). ctDNA detection at baseline was 8% and 17% at any timepoint. Among pts who were baseline ctDNA negative, 10% became positive on tx and among pts who were baseline ctDNA positive, 59% remained persistently positive on tx. Among pts with ctDNA positivity, 87% had an IDFS event in comparison to 15% with persistent ctDNA negative status during the study. Conclusions: In a pt subset from monarchE enriched for IDFS events, ctDNA detection was relatively infrequent (<20%); however, its detection at any time during the 24 months of study therapy was adversely prognostic. As compared to pts who remained ctDNA positive, pts who had clearance of ctDNA on therapy had lower risk of IDFS events, but the event risk still remained clinically meaningful in thesepts. Previously presented at ASCO 2024. The Breast 80S (2025) 103902 https://doi.org/10.1016/j.breast.2025.103902 P009 Adjuvant Abemaciclib Plus Endocrine Therapy for HR+, HER2-, High-risk Early Breast cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-year Efficacy Outcomes V. André1, N. Harbeck2, P. Rastogi3, J. O’Shaughnessy4, F. Boyle5, J. Cortes6, H.S. Rugo7, M.P. Goetz8, E. Hamilton9, C.-S. Huang10, E. Senkus11, A. Tryakin12, P. Neven13, J. Huober14, R.Wei1,M.Munoz1, B.S. Antonio1, A. Shahir1,M.Martin15, S. Johnston16. 1Eli Lilly and Company, Indianapolis, IN, United States; 2Breast Centre, Department of Gynecology and Obstetrics, Comprehensive Cancer Centre München, LMU University Hospital, Munich, Germany; 3UPMC Hillman Cancer Center and NSABP Foundation, Pittsburgh, PA, United States; 4Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, United States; 5Sydney Medical School, University of Sydney, Sydney, NSW, Australia; 6International Breast Cancer Center (IBCC), Quironsalud Group, Barcelona, Spain; 7Department of Medicine, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, United States; 8Mayo Clinic, Rochester, MN, United States; 9Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, United States; 10Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan; 11Medical University of Gdańsk, Gdańsk, Poland; 12N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation; 13Multidisciplinary Breast Center, University Hospitals Leuven, Louvain, Belgium; 14Breast Center, Kantonsspital St. Gallen, St. Gallen, Switzerland; 15Hospital General Universitario Gregorio Marañon, Universidad Complutense, CIBERONC, GEICAM, Madrid, Spain; 16The Royal Marsden NHS Foundation Trust, London, United Kingdom Goals: Two years (yrs) of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-yr treatment (tx) period in patients (pts) with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-yr efficacy results from a prespecified overall survival (OS) interim analysis. Methods: Pts were randomized (1:1) to receive ET for at least 5 yrs ± abemaciclib for 2 yrs (tx period). High-risk EBC was defined as either ≥4 positive axillary lymph nodes (ALN) or 1–3 ALN with Grade 3 disease and/or tumor≥5 cm (Cohort 1). A smaller group of pts were enrolled with 1–3+ ALN and central Ki67≥20% (Cohort 2). The intentto-treat (ITT) population consisted of Cohort 1 (5120 pts) and Cohort 2 (517 pts). OS in the ITT population was tested for statistical significance in the gated strategy. Hazard ratios (HR) were estimated using Cox proportional hazard model. Results: In the ITT population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with a HR of 0.680 (95% CI: 0.599, 0.772) for IDFS and 0.675 (95% CI: 0.588, 0.774) for DRFS. This persistence of abemaciclib benefit translated to continued separation of the KM curves resulting in a 5-yr absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with IDFS/ DRFS rates of 6.0%/5.3% at 4 yrs and 4.8%/4.1% at 3 yrs. Tx benefit in Cohort 1 was consistent with ITT. No new safety signals were observed. There continued to be fewer deaths in the abemaciclib plus ET arm compared to the ET arm (208 vs 234; HR 0.903; p = 0.284); significance was not met. Conclusions: At the pivotal 5-yr mark for adjuvant EBC trials, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence well beyond the completion of tx. The increasing absolute improvement at 5 yrs is consistent with a carryover effect and further supports the use of abemaciclib in pts with high-risk EBC. OS data are evolving in favor of abemaciclib arm, and follow-up continues. 19th St.Gallen International Breast Cancer Conference / The Breast 80S (2025) S1–S188 S5
Originally presented at European Society for Medical Oncology 48th Congress - ESMO 2023 and Rastogi P et al. 2024. Journal of Clinical Oncology; JCO 0, JCO.23.01994. The Breast 80S (2025) 103903 https://doi.org/10.1016/j.breast.2025.103903 P012 5-year vs 10-year Hormone Therapy: Comparison of Recurrence in Patients with Luminal A and Luminal B Breast Cancer D. Alexandrou1, M. Papakonstantinou1, G. Kolympa1, V.N. Papadopoulos1. 11st Surgical Department, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece Goals: Breast cancer (BC) is the most common malignancy diagnosed in women. Surgical resection remains the cornerstone of the treatment, however patients with estrogen receptor positive (ER+) breast cancer have largely benefited from adjuvant hormone therapy (HT). Even though 5 years of HT is the current mainstay for early-stage breast cancer, the extension of its duration has become popular over the past years. Our goal is to assess the recurrence rate after 5 years and after 10 years of adjuvant HT administration in patients with luminal type BC. Methods: A thorough literature search was conducted in PubMed and clinicaltrials.gov for studies including adult patients with luminal type A and type B breast cancer treated with surgery and adjuvant hormone therapy. The search was completed by two independent reviewers according to the PRISMA checklist. Results: Eleven studies were included in this systematic review. In 4 of them, 2,246 patients were analyzed after receiving adjuvant HT for up to 5 years. Hormone therapy for 5 years was shown to prevent recurrence from BC without exposing patients to significant adverse events. Whatsmore patients receiving HT could avoid chemotherapy even in the setting of lymph node metastasis. Both non-receiving and early discontinuation of HT were related to a worse recurrence-free survival (RFS). On the other hand, six clinical trials, including 25,481 patients, studied the effects of extending HT for more than 5 years. The results showed improved RFS rates after 10 years of receiving HT. Similar results have been reported regarding the 10-year administration of tamoxifen in 3 large clinical trials (the ATLAS, the aTTom and the extended SOFT trials). However, one of the included studies compared 5-year extension to 2-year extension of HT and showed that extending HT by 5 years not only provided no advantage over extension by 2 years but also increased the risk of adverse events, such as bone fractures. Given the low recurrence risk (<10%) identified among 8,501 patients after receiving HT for 5 years, some researchers suggested that certain patients with stage I and stage II BC could safely discontinue and therefore avoid the long-term effects of exposure to HT. Conclusions: Hormone therapy is an essential adjunct to the treatment of patients with luminal A and luminal B type BC. Even though it is not free of complications, extending the duration of HT in carefully selected patients for up to 10 years could further improve their recurrence-free survival. The Breast 80S (2025) 103904 https://doi.org/10.1016/j.breast.2025.103904 P013 Validation of the CTS5 in four prospective, multicenter, randomized ABCSG trials K.Wimmer1,2, D. Hlauschek3,M. Balic4, G. Pfeiler5,2, R. Greil6,7,8, C.F Singer5,2, S. Halper9, G. Steger10, C. Suppan4, S.P. Gampenrieder6,7,8, R. Helfgott11, D. Egle12, M. Filipits13, R. Jakesz2, L. Sölkner3, C. Fesl3,M. Gnant3,2, F. Fitzal14, on behalf of the Austrian Breast & Colorectal Cancer Study Group. 1Department of Surgery, Medical University of Vienna, Vienna, Austria; 2Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; 3Austrian Breast & Colorectal Cancer Study Group, Vienna, Austria; 4Department of Oncology, Medical University of Graz, Graz, Austria; 5Department of Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria; 6Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria; 7Salzburg Cancer Research Institute-CCCIT, Salzburg, Austria; 8Cancer Cluster Salzburg, Salzburg, Austria; 9Deceased, Wiener Neustadt, Austria; 10Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria; 11Department of Surgery, Ordensklinikum Linz - Sisters of Charity, Linz, Austria; 12Department of Gynecology, Medical University Innsbruck, Innsbruck, Austria; 13Center for Cancer Research, Medical University of Vienna, Vienna, Austria; 14Department of Surgery and Breast Health Center, Hanusch Krankenhaus, Vienna, Austria Goals: The Clinical Treatment Score post-5 years (CTS5) is a clinicopathological tool that estimates late distant recurrence (LDR) in hormone receptor-positive (HR+) breast cancer patients after 5 years of adjuvant endocrine therapy (ET). Intended as a prognostic algorithm, its predictive value regarding ET extension remains questionable. Methods: The calculation of the score was performed in 4,931 patients from four prospective randomized ABCSG trials (ABCSG-6, −6a, −8 and −16) with 250 LDR events. We investigated the prognostic power, the calibration accuracy as well as the predictive value of the score. Time to LDR was analyzed with Cox regression models. Results: In our cohorts the CTS5 provided prognostic information, regardless whether it was used either as a continuous or categorical score. In the ABCSG-8 cohort (n = 2,054) as well as the combined ABCSG-6+8 cohort (n = 3,308) an increasing continuous score was significantly associated with an increased risk of LDR. The categorical CTS5 provided prognostic information: CTS5 high-risk patients had significantly higher rates of LDR compared to low- or intermediaterisk patients. The score slightly tended to overestimate the LDR risk, irrespective of the predicted risk. Although the predictive value could not be confirmed on the relative scale, an absolute risk reduction for LDR events 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 ten instead of seven years. Conclusions: The CTS5 is a valid tool for LDR risk stratification in women with HR+BC. In order to answer the question of whether patients will benefit from extended ET, the score has to be used with caution since a statistically significant predictive value was not observed. The Breast 80S (2025) 103905 https://doi.org/10.1016/j.breast.2025.103905 Poster Abstracts / The Breast 80S (2025) S1–S188 S6
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