Axillary Surgery in Breast Cancer — Primary Results of the INSEMA Trial

Authors: Toralf Reimer, Ph.D., Angrit Stachs, Ph.D., Kristina Veselinovic, M.D., Thorsten Kühn, Ph.D., Jörg Heil, Ph.D. , Silke Polata, M.D., Frederik Marmé, Ph.D., Thomas Müller, Ph.D., Guido Hildebrandt, Ph.D., David Krug, Ph.D., Beyhan Ataseven, Ph.D., Roland Reitsamer, Ph.D., Sylvia Ruth, M.D., Carsten Denkert, Ph.D., Inga Bekes, Ph.D., Dirk-Michael Zahm, M.D., Marc Thill, Ph.D., Michael Golatta, Ph.D., Johannes Holtschmidt, M.D., Michael Knauer, Ph.D., Valentina Nekljudova, Ph.D., Sibylle Loibl, Ph.D., and Bernd Gerber, Ph.D.

Published December 12, 2024, N Engl J Med 2025;392:1051-1064;  DOI: 10.1056/NEJMoa2412063

The Intergroup-Sentinel-Mamma (INSEMA) trial (NCT02466737, GBG75, ABCSG43) was a multicentre, prospective, randomized, non-inferiority study assessing the safety of omitting surgical axillary staging in patients with early-stage (cT1-T2), clinically and radiologically node-negative (cN0) breast cancer undergoing breast-conserving surgery and whole-breast radiotherapy. Conducted across 151 sites in Germany and Austria, 4,858 patients were randomized in a 1:4 ratio to either omission of sentinel lymph node biopsy (SLNB; n=962) or standard SLNB (n=3,896).  Patients with 1–3 macrometastases in the SLNB were further randomized to axillary lymph node dissection or no additional surgery. 

In this paper, analysis of the primary outcomes (invasive disease-free survival, iDFS, and overall survival, OS) is presented. After a median follow-up of 6 years, 5-year iDFS was 91.9% (95% CI, 89.9–93.5) in the omission group versus 91.7% (95% CI, 90.8–92.6) in the SLNB group with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), demonstrating non-inferiority.  5-year OS was 98.2% (95% CI 97.1%-98.9%) in the omission group vs. 96.9% (95% CI 96.3%-97.5%) for SLNB.  There were absolute differences between the omission group and the SLNB group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%).  Complication rates, including lymphedema, restricted shoulder mobility, and pain, were lower in the omission group.

The authors conclude that axillary surgery may be safely omitted in selected patients with low-risk, node-negative early breast cancer.  However, as only 10% of participants had T2 tumours or were under the age of 50, respectively, conclusions for these subgroups remain limited.  Omission of SLNB may be most suitable for patients >50 years old with hormone receptor-positive, HER2-negative, grade 1-2, T1 tumours.

Summary written by Aliaa Shamardal, ST6 Breast Surgery, Glenfield Hospital, Leicester.