Real-world evidence on risk of recurrence (ROR) in patients (pts) with node-negative (N0) and node-positive HR+/HER2– early breast cancer (EBC) from US electronic health records (EHR)

BackgroundWhile a CDK4/6 inhibitor is approved for high-risk node-positive HR+/HER2− EBC, its use is not approved for N0 disease. Pts with N0 disease and high-risk features may particularly be at risk for disease recurrence, but contemporary information on ROR and mortality is limited. Here, real-world data was used to estimate risk for pts with HR+/HER2− EBC.MethodsPts aged ≥18 years with AJCC stage I-III HR+/HER2− EBC in the US Flatiron Health EBC de-identified EHR-derived database (2011-2023) were included. ROR and all-cause mortality from time of diagnosis were assessed descriptively across nodal status, including a subgroup of pts with N0 disease with high-risk characteristics (N0 high-risk) as defined by NATALEE eligibility criteria: T4N0, T3N0, or T2N0 with additional criteria (grade [G]2 with Ki-67≥20% or high genomic risk, or G3).ResultsOf 15,017 pts, 7564 met study criteria: 5557 (73.5%) N0 disease [679 (12.2%) N0 high-risk], 1560 (20.6%) N1, and 447 (5.9%) N2-3. Overall median follow-up was 79.1 (45.7, 113.6) mo. Median age was 65, 62, 61, and 61 y in N0, N0 high-risk, N1, and N2-3 groups, respectively. In total, 94.7%, 86.9%, 90.8%, and 85.0% received (neo)adjuvant endocrine therapy; 15.8%, 47.4%, 45.0%, and 68.9% received (neo)adjuvant chemotherapy. Most pts were postmenopausal (76.2%, 68.6%, 67.1%, and 69.1%). ROR and mortality were positively associated with nodal status (P<.0001). N1 and N0 high-risk disease had numerically similar and considerable risk of overall and distant recurrence and mortality across time points (Table). Table: 292P N0 N0 high-risk N1 N2-3 Incidence (95% CI), % Overall recurrence 3-y 2.7 (2.2-3.2) 8.1 (6.0-10.7) 7.5 (6.2-9.0) 21.7 (17.7-26.3) 5-y 4.7 (4.1-5.5) 12.6 (9.9-16.1) 12.8 (11.0-15.0) 33.8 (28.8-39.4) 7-y 7.2 (6.3-8.3) 16.9 (13.3-21.3) 17.1 (14.7-19.8) 43.7 (37.9-50.0) Distant recurrence 3-y 1.5 (1.1-1.9) 6.0 (4.2-8.4) 5.5 (4.3-6.8) 19.7 (15.9-24.2) 5-y 2.8 (2.3-3.4) 9.4 (7.0-12.4) 10.0 (8.3-12.0) 31.1 (26.2-36.7) 7-y 4.3 (3.6-5.2) 13.6 (10.3-17.8) 13.7 (11.5-16.2) 40.1 (34.4-46.4) Mortality 3-y 2.5 (2.1-3.0) 3.7 (2.4-5.6) 3.8 (2.9-5.0) 11.3 (8.5-15.0) 5-y 5.8 (5.0-6.6) 8.1 (5.9-11.1) 9.1 (7.6-11.0) 21.5 (17.4-26.4) 7-y 11.2 (10.0-12.5) 16.8 (13.0-21.4) 15.9 (13.5-18.6) 34.9 (29.5-41.0) ConclusionsThis contemporary real-world analysis revealed considerable ROR across pts with positive nodal status and pts with N0 high-risk disease. N0 high-risk had 3.2× risk of distant recurrence and 1.5× risk of mortality at 7 y vs N0. Treatments to improve outcomes are needed, including for pts with N0 high-risk disease.Editorial acknowledgementEditorial assistance in the writing of the abstract was provided by Safiyya Ali, MSc, CMPP of Nucleus Global.Legal entity responsible for the studyNovartis Pharmaceuticals Corporation.FundingNovartis Pharmaceuticals Corporation.DisclosureK. Jhaveri: Financial Interests, Personal and Institutional, Advisory Board: Novartis, Astrazeneca, Pfizer, Genentech/Roche, Lilly Pharmaceuticals/Loxo Oncology, Gilead; Financial Interests, Personal and Institutional, Other, Consultant: Novartis, Astrazeneca, Pfizer, Genentech/Roche, Lilly Pharmaceuticals/Loxo Oncology, Gilead; Financial Interests, Personal and Institutional, Funding: Novartis, Astrazeneca, Pfizer, Genentech/Roche, Lilly Pharmaceuticals/Loxo Oncology, Gilead; Financial Interests, Personal, Advisory Board: BMS, Jounce Therapeutics, Taiho Oncology, AbbVie, Eisai, Blueprint Medicines, Seattle Genetics, Daiichi Sankyo, Olema Pharmaceuticals, Sun Pharma Advanced Research Company Ltd, Menarini/Stemline; Financial Interests, Personal, Other, Consultant: BMS, Jounce Therapeutics, Taiho Oncology, AbbVie, Eisai, Blueprint Medicines, Seattle Genetics, Daiichi Sankyo, Olema Pharmaceuticals, Sun Pharma Advanced Research Company Ltd, Menarini/Stemline; Financial Interests, Institutional, Funding: Debio Pharmaceuticals, Zymeworks, PUMA Biotechnology, Merck Pharmaceuticals, Context Therapeutics. G. Curigliano: Financial Interests, Personal, Advisory Board: Roche, Novartis, Lilly, Pfizer, AstraZeneca, Daichii Sankyo, Ellipsis, Veracyte, Exact Science, Celcuity, Merck, BMS, Gilead, Sanofi. L.M. Spring: Financial Interests, Personal, Other: Novartis, Merck, Phillips. J. Gligorov: Financial Interests, Personal and Institutional, Other, Clinical Trials: Roche-Genentech, Novartis, Eisai, Exact Science, Pfizer, Lilly; Financial Interests, Personal and Institutional, Other, Travel support: Roche-Genentech, Novartis, Eisai, Exact Science, Pfizer, Mylan, Lilly, Pierre Fabre; Financial Interests, Personal and Institutional, Advisory Board: Roche-Genentech, Novartis, Eisai, Exact Science, Pfizer, Mylan, Lilly, Pierre Fabre; Financial Interests, Personal and Institutional, Speaker’s Bureau: Roche-Genentech, Novartis, Eisai, Exact Science, Pfizer, Mylan, Lilly, Pierre Fabre; Financial Interests, Personal, Other, Clinical Trials: Daiichi Sankyo, MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, MSD, Astrazeneca; Financial Interests, Personal, Speaker’s Bureau: Astrazeneca. N. Harbeck: Financial Interests, Personal, Other, Consulting: Novartis, Pfizer, Roche, Sandoz/Hexal, Gilead, Seagen, Sanofi; Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, MSD, Pierre-Fabre, Roche, Gilead, Seagen, Sanofi, Viatris, Medscape, Onkowissen, Zuelligpharma, Aptitude Health, Art Tempi; Financial Interests, Institutional, Funding: Novartis, Lilly, AstraZeneca, Daiichi Sankyo, MSD, Pierre-Fabre, Roche, West German Study Group, Seagen, Palleos, TRIO, BMS; Financial Interests, Personal, Advisory Board: Pfizer, Sandoz/Hexal, Gilead, Seagen, Sanofi; Financial Interests, Personal, Leadership Role, Co director WST: West German Study Group; Non-Financial Interests, Member: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Non-Financial Interests, Leadership Role, Founding Editor: BreastCare Journal. D. Juric: Financial Interests, Institutional, Funding: Pfizer, Amgen, InventisBio, Arvinas, Takeda, Blueprint, Astrazeneca, Ribon Therapeutics, Infinity. H. Owusu: Financial Interests, Personal, Full or part-time Employment: Novartis. M. Akdere: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks or ownership: Novartis. J. Kim: Financial Interests, Institutional, Other, Employee of Genesis Research, whom Novartis has paid fees for consulting: Novartis. F. Cardoso: Financial Interests, Personal, Advisory Board, Consulting: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, EISAI, GE Oncology, Genentech, GSK, Macrogenics, Medscape, Merck-Sharp, Merus, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Teva, Seagen, Debiopharm, Gilead, Iqvia, Touchime. All other authors have declared no conflicts of interest.