Evidence-Based Management of High-Risk Early Breast Cancer in 2025

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The evidence-based management of high-risk early breast cancer in 2025:
    • Is highly individualized:
    • It is guided by tumor biology, clinical risk factors, and genomic profiling
  • High-risk features include:
    • Large tumor size (≥ 2 cm)
    • Nodal involvement:
      • Especially ≥ 4 positive nodes or 1 to 3 nodes with additional high-risk features:
        • High grade
        • Lymphovascular invasion
        • High-risk genomic signatures (e.g., 21-gene, 70-gene, PAM50 assays)
  • Multigene assays are routinely used to refine risk stratification and guide chemotherapy decisions, especially in HR-positive / HER2-negative disease:
    • HR-positive / HER2-negative:
      • All patients receive adjuvant endocrine therapy
      • For those with high-risk features (≥ 4 positive nodes, or 1 to 3 nodes with grade 3 or tumor ≥ 5 cm), high Ki-67:
        • A CDK4/6 inhibitor (abemaciclib or ribociclib) is added to endocrine therapy
      • Adjuvant olaparib is considered for patients with germline BRCA mutations and high-risk HER2-negative disease
      • Chemotherapy is recommended for those with high clinical or genomic risk
    • HER2-positive:
      • High-risk patients receive neoadjuvant or adjuvant chemotherapy plus trastuzumab ± pertuzumab
      • If residual disease remains after neoadjuvant therapy:
        • Ado-trastuzumab emtansine is indicated
      • Endocrine therapy is added for HR-positive /HER2-positive cases
    • Triple-negative:
      • Neoadjuvant chemotherapy plus pembrolizumab is standard for high-risk disease
      • For residual disease or BRCA mutation, adjuvant pembrolizumab and / or capecitabine or olaparib are considered
  • Radiation therapy (whole breast or postmastectomy) is indicated for:
    • Node-positive or other high-risk features after breast-conserving surgery
    • Axillary surgery is being de-escalated in select low-risk patients:
      • With omission of sentinel lymph node biopsy increasingly supported
  • Supportive care includes:
    • Bisphosphonates or denosumab:
      • For bone health in postmenopausal or high-risk patients
  • Survivorship strategies now include:
    • Emerging liquid biopsy-guided surveillance for earlier detection of recurrence:
      • Though this is still under investigation
  • Areas needing further evidence include:
    • Optimal sequencing and integration of adjuvant targeted therapies (CDK4/6 inhibitors, PARP inhibitors, immunotherapy) and the role of liquid biopsy in routine follow-up
  • References:
    • Breast Cancer. National Comprehensive Cancer Network. Updated 2025-04-17.
    • Outcomes Based on Risk-Adapted Adjuvant Therapy in Postmenopausal Women With Early Breast Cancer: A Nationwide, Prospective Cohort Study by the Danish Breast Cancer Group. Jensen MB, Torpe E, Teunissen Z, et al. The Lancet. Oncology. 2025;26(5):654-662. doi:10.1016/S1470-2045(25)00085-3.
    • Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update. Andre F, Ismaila N, Allison KH, et al. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2022;40(16):1816-1837. doi:10.1200/JCO.22.00069.
    • FDA Orange Book. FDA Orange Book.
      State-of-the-art management of HER2-negative early breast cancer: Treatment patterns among healthcare professionals and concordance with expert recommendations. Becker M, Abraham J, Kalinsky K, et al. Journal of Clinical Oncology. 2023;41(Suppl 16):553. doi:10.1200/JCO.2023.41.16_suppl.553.
    • Current treatment patterns for early breast cancer among healthcare professionals and concordance with expert recommendations: Analysis of an online interactive decision support tool. Timothy Quill, Kristen Rosenthal and Megan Cartwright. Journal of Clinical Oncology. 2025;43(Suppl 16):1550. doi:10.1200/JCO.2025.43.16_suppl.1550.
      Emerging Targeted Therapies for Early Breast Cancer. Schlam I, Tarantino P, Morganti S, et al. Drugs. 2022;82(14):1437-1451. doi:10.1007/s40265-022-01781-5.
    • How We Treat HR-positive, HER2-negative Early Breast Cancer. Lopez-Tarruella S, Echavarria I, Jerez Y, et al. Future Oncology (London, England). 2022;18(8):1003-1022. doi:10.2217/fon-2021-0668.
    • Tailoring Treatment to Cancer Risk and Patient Preference: The 2025 St Gallen International Breast Cancer Consensus Statement on Individualizing Therapy for Patients With Early Breast Cancer. Burstein HJ, Curigliano G, Gnant M, et al. Annals of Oncology : Official Journal of the European Society for Medical Oncology. 2025;:S0923-7534(25)04718-0. doi:10.1016/j.annonc.2025.09.007.
    • Therapy of Early Breast Cancer: Current Status and Perspectives. Tauber N, Amann N, Dannehl D, et al. Archives of Gynecology and Obstetrics. 2025;:10.1007/s00404-025-08028-0. doi:10.1007/s00404-025-08028-0.
    • The SURVIVE study: Standard surveillance vs. intensified liquid biopsy-based surveillance in early breast cancer survivors. Schäffler H, Huesmann S, Friedl T, et al. Journal of Clinical Oncology. 2025;43(Suppl 16):TPS621. doi:10.1200/JCO.2025.43.16_suppl.TPS621.
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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