The estimates presented are derived from published data [35, 37]. For abemaciclib, the estimates are based on FDA-approved eligibility criteria. They are intended to illustrate the potential clinical implications of nodal staging. They have not been prospectively validated and should not be interpreted as predictive estimates. NNS: number needed to stage; CDK4/6: cyclin-dependent kinase 4 and 6; LN: lymph node.
Declarations
Acknowledgments
During the preparation of this work, the authors used ChatGPT (OpenAI) to assist in the design and visual layout of Figure 1. The scientific concept, content, clinical recommendations, and final figure were conceived, reviewed, and edited by the authors, who take full responsibility for the final content of the publication.
Author contributions
WT, SC: Conceptualization, Investigation, Data curation, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
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References
Halsted WS. I. The Results of Operations for the Cure of Cancer of the Breast Performed at the Johns Hopkins Hospital from June, 1889, to January, 1894.Ann Surg. 1894;20:497–555. [DOI] [PubMed] [PMC]
Halsted WS. I. The Results of Radical Operations for the Cure of Carcinoma of the Breast.Ann Surg. 1907;46:1–19. [DOI] [PubMed] [PMC]
Kardeh S, Kardeh B. Avicenna’s Concepts on Cancer Metastasis from the 11th Century.Galen Med J. 2019;8:e1292. [PubMed] [PMC]
Récamier JCA. Recherches sur le traitement du cancer, par la compression méthodique simple ou combinée, et sur l’histoire générale de la même maladie. 2nd ed. Paris: Gabon; 1829.
Verboven G, Huizing MT, Weijer M, Ysebaert D, Ramadhan A, Wyngaert T, et al. Long-Term Survival of Metachronous Isolated Adrenal Metastasis in Luminal Breast Cancer: A Case Report and Literature Review.Cureus. 2025;17:e78142. [DOI] [PubMed] [PMC]
Paget S. THE DISTRIBUTION OF SECONDARY GROWTHS IN CANCER OF THE BREAST.The Lancet. 1889;133:571–3. [DOI]
Ewing J. Neoplastic Diseases: A Treatise on Tumors. 3rd ed. Philadelphia: W.B. Saunders; 1928.
Banys M, Hartkopf AD, Krawczyk N, Kaiser T, Meier-Stiegen F, Fehm T, et al. Dormancy in breast cancer.Breast Cancer (Dove Med Press). 2012;4:183–91. [DOI] [PubMed] [PMC]
Truskowski K, Amend SR, Pienta KJ. Dormant cancer cells: programmed quiescence, senescence, or both?Cancer Metastasis Rev. 2023;42:37–47. [DOI] [PubMed] [PMC]
Anderson S. A Short History of Bernard Fisher’s Contributions to Randomized Clinical Trials.Clin Trials. 2022;19:127–36. [DOI] [PubMed] [PMC]
Fisher B, Redmond C, Fisher ER, Bauer M, Wolmark N, Wickerham DL, et al. Ten-Year Results of a Randomized Clinical Trial Comparing Radical Mastectomy and Total Mastectomy with or without Radiation.N Engl J Med. 1985;312:674–81. [DOI] [PubMed]
Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-Five-Year Follow-up of a Randomized Trial Comparing Radical Mastectomy, Total Mastectomy, and Total Mastectomy Followed by Irradiation.N Engl J Med. 2002;347:567–75. [DOI] [PubMed]
Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic Mapping and Sentinel Lymphadenectomy for Breast Cancer.Ann Surg. 1994;220:391–401. [DOI] [PubMed] [PMC]
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Ashikaga T, et al. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial.Lancet Oncol. 2007;8:881–8. [DOI] [PubMed]
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial.Lancet Oncol. 2010;11:927–33. [DOI] [PubMed] [PMC]
Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, et al. Randomized Multicenter Trial of Sentinel Node Biopsy Versus Standard Axillary Treatment in Operable Breast Cancer: The ALMANAC Trial.J Natl Cancer Inst. 2006;98:599–609. [DOI] [PubMed]
Galimberti V, Cole BF, Viale G, Veronesi P, Vicini E, Intra M, et al.; International Breast Cancer Study Group Trial 23-01. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial.Lancet Oncol. 2018;19:1385–93. [DOI] [PubMed]
Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23–01): a phase 3 randomised controlled trial.Lancet Oncol. 2013;14:297–305. [DOI] [PubMed] [PMC]
Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, et al. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial.JAMA. 2017;318:918–26. [DOI] [PubMed] [PMC]
Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial.Lancet Oncol. 2014;15:1303–10. [DOI] [PubMed] [PMC]
Sávolt Á, Péley G, Polgár C, Udvarhelyi N, Rubovszky G, Kovács E, et al. Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: A randomized, single centre, phase III, non-inferiority trial.Eur J Surg Oncol. 2017;43:672–79. [DOI] [PubMed]
de Boniface J, Filtenborg Tvedskov T, Rydén L, Szulkin R, Reimer T, Kühn T, et al. Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.N Engl J Med. 2024;390:1163–75. [DOI] [PubMed]
Martelli G, Miceli R, Daidone MG, Vetrella G, Cerrotta AM, Piromalli D, et al. Axillary Dissection Versus No Axillary Dissection in Elderly Patients with Breast Cancer and No Palpable Axillary Nodes: Results After 15 Years of Follow-Up.Ann Surg Oncol. 2011;18:125–33. [DOI] [PubMed] [PMC]
Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, et al. Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up of CALGB 9343.J Clin Oncol. 2013;31:2382–7. [DOI] [PubMed] [PMC]
Gentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, et al.; SOUND Trial Group. Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial.JAMA Oncol. 2023;9:1557–64. [DOI] [PubMed] [PMC]
Reimer T, Stachs A, Veselinovic K, Kühn T, Heil J, Polata S, et al. Axillary Surgery in Breast Cancer — Primary Results of the INSEMA Trial.N Engl J Med. 2025;392:1051–64. [DOI] [PubMed]
Schipper RJ, van Roozendaal LM, Wintraecken VM, Simons JM, Moossdorff M, Luiten EJT, et al.; BOOG 2013-08 Study Group. Abstract GS2-11: Omission of sentinel lymph node biopsy in clinically T1-2 node-negative breast cancer patients treated with breast-conserving therapy: results of the Dutch BOOG 2013-08 randomized controlled trial after a median follow-up of 5 years.Clin Cancer Res. 2026;32:GS2–11. [DOI]
van Roozendaal LM, Vane MLG, van Dalen T, van der Hage JA, Strobbe LJA, Boersma LJ, et al. Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).BMC Cancer. 2017;17:459. [DOI] [PubMed] [PMC]
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.N Engl J Med. 2018;379:111–21. [DOI] [PubMed] [PMC]
Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer.N Engl J Med. 2021;385:2336–47. [DOI] [PubMed] [PMC]
Akrida I, Michalopoulos NV, Lagadinou M, Papadoliopoulou M, Maroulis I, Mulita F. An Updated Review on the Emerging Role of Indocyanine Green (ICG) as a Sentinel Lymph Node Tracer in Breast Cancer.Cancers (Basel). 2023;15:5755. [DOI] [PubMed] [PMC]
Wanis KN, Mitchell MP, Giordano SH, Litton JK, Shaitelman SF, Tamirisa N, et al. Implications of omitting sentinel lymph node biopsy on adjuvant decision making for patients with small breast cancers.Cancer. 2025;131:e35910. [DOI] [PubMed] [PMC]
Heidinger M, Zwimpfer TA, Halbeisen FS, Maggi N, Frevert ML, Kiblawi R, et al. Omission of sentinel lymph node biopsy in early stage luminal breast cancer: impact on adjuvant CDK4/6 inhibitor recommendation and oncological outcomes.Breast. 2026;85:104641. [DOI] [PubMed] [PMC]
Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group.J Natl Cancer Inst. 2011;103:1656–64. [DOI] [PubMed] [PMC]
Siziopikou KP, Anderson SJ, Cobleigh MA, Julian TB, Arthur DW, Zheng P, et al. Preliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43.Breast Cancer Res Treat. 2013;142:415–21. [DOI] [PubMed] [PMC]
O’Keefe TJ, Blair SL, Hosseini A, Harismendy O, Wallace AM. HER2-Overexpressing Ductal Carcinoma In Situ Associated with Increased Risk of Ipsilateral Invasive Recurrence, Receptor Discordance with Recurrence.Cancer Prev Res. 2020;13:761–72. [DOI] [PubMed]
Cobleigh MA, Anderson SJ, Siziopikou KP, Arthur DW, Rabinovitch R, Julian TB, et al. Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial.J Clin Oncol. 2021;39:2367–74. [DOI] [PubMed] [PMC]
Tjalma WAA. Should nodal staging include an “i” for imaging to improve selection for sentinel node biopsy omission in early breast cancer?Eur J Obstet Gynecol Reprod Biol. 2026;325:115335. [DOI] [PubMed]
Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.JAMA. 2011;305:569–75. [DOI] [PubMed]