Abstract
The sub-study of the INSEMA trial (randomization-2) compares completion axillary lymph node dissection (cALND) with sentinel lymph node biopsy (SLNB) alone in cN0 patients with T1/T2 invasive breast cancer and one to three sentinel node macrometastases undergoing upfront breast-conserving surgery. The key secondary objective is to assess whether the SLNB-alone arm is non-inferior to cALND in terms of invasive disease-free survival (iDFS). Finally, 485 patients were recruited, and 386 patients (cALND: N = 169, SLNB alone: N = 217) were included in the per-protocol set. The median follow-up is 74.2 months. The 5-year iDFS analysis in the per-protocol set demonstrates a non-significant difference between study arms, with a hazard ratio (HR) of 1.69 (95% CI: 0.98-2.94) for SLNB alone compared to cALND. The 5-year iDFS rates are 86.6% (81.0%-90.7%) in the SLNB-alone arm and 93.8% (88.7%-96.6%) in the cALND arm (P = 0.058). The 5-year overall survival rates are 94.9% (90.6%-97.2%) in the SLNB-alone arm and 96.2% (91.7%-98.3%) in the cALND arm (P = 0.663). Locoregional recurrences (LRR) were infrequent, with 5-year incidence rates of 1.1% versus 0.0% (P = 0.405) in the SLNB-alone arm compared to cALND. In summary, no significant differences were observed between SLNB alone versus cALND for iDFS, overall survival, and LRR. Trial registration number: NCT02466737
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Acknowledgements
The INSEMA trial was sponsored by the University Medicine Rostock (Germany) and financed by the Deutsche Krebshilfe under grant numbers #110580 and #70110580 (German Cancer Aid, Bonn, Germany). The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript. The locoregional subboard of GBG (Neu-Isenburg, Germany) overlooked the trial; the ABCSG (Vienna, Austria) coordinated the Austrian study sites. Oral presentation at the San Antonio Breast Cancer Symposium 2025.
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T.R., A.S., K.V., T.K., J.H., S.P., F.M., E.T., G.H., D.K., B.A., R.R., S.R., C.D., I.B., N.S., M.T., H.S., T.M., M.G., D.Z., J.H., M.K., V.N., S.L., and B.G. contributed to the study design, collection, and documentation of data. T.R., A.S., T.K., D.K., J.H., V.N., S.L., and B.G. wrote the main manuscript text, and V.N. prepared Figs. 1–3. V.N. was responsible for statistical analysis. T.R., A.S., K.V., T.K., J.H., S.P., F.M., E.T., G.H., D.K., B.A., R.R., S.R., C.D., I.B., N.S., M.T., H.S., T.M., M.G., D.Z., J.H., M.K., V.N., S.L., and B.G. reviewed and approved the final manuscript.
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Reimer, T., Stachs, A., Veselinovic, K. et al. Axillary surgery in patients with sentinel node macrometastases: secondary results of the randomized INSEMA trial. npj Breast Cancer (2026). https://doi.org/10.1038/s41523-026-00902-7
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DOI: https://doi.org/10.1038/s41523-026-00902-7
