Randomised controlled trialindependent cross-checkabstract checked★ key study I-SRC-106 in-depth review
Skipping armpit lymph-node surgery in small breast cancers
Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial.
Overview
Reimer T et al.. N Engl J Med 2025 · PMID 39665649 · DOI 10.1056/NEJMoa2412063
Women with small breast cancers who had no lymph-node surgery did as well over 6 years as those who had a sentinel-node biopsy, with less arm swelling.
Does the study support the specific claim? Partly · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test omitting lymph-node surgery
- How was the study done?
Randomised trial
- How many people, animals or samples were studied?
5502 women
- What was actually found?
No worse survival without node surgery; fewer arm problems
- How large was the observed effect?
5-y iDFS 91.9% vs 91.7%; HR 0.91
- What do the results mean in everyday life?
Less lymph-node surgery is often possible
- What are the study's limitations?
Mostly small tumours
- What does it say about Elawady's specific claim?
Supports less node surgery but tumour was always removed
- Do the results apply to Germany and Europe?
High
- What can explicitly not be concluded from this study?
Whether tumour surgery can be skipped (it cannot be concluded)
Scientific in-depth review
1. Full reference
- Authors
- Reimer T et al.
- Journal
- N Engl J Med
- Year
- 2025
- Identifier
- PMID 39665649 DOI 10.1056/NEJMoa2412063
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works record checked
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Funded by German Cancer Aid; no COI statement in PubMed record.
2. Research question
Can surgical axillary staging (sentinel-node biopsy) be omitted in breast-conserving therapy without compromising survival?
3. Study design and population
- Study design
- Randomised controlled trial – Prospective randomised non-inferiority trial (INSEMA), per-protocol primary analysis
- Population
Clinically node-negative T1-T2 invasive breast cancer, breast-conserving surgery
- Country
Germany and Austria
- Period
Median follow-up 73.6 months
- Sample size
5502 randomised (1:4); per-protocol 4858
- Inclusion and exclusion criteria
cN0, tumour <=5 cm, breast-conserving surgery planned
4. Methods and endpoints
- Exposure / intervention
No axillary surgery
- Comparator
Sentinel-lymph-node biopsy
- Endpoints
Invasive disease-free survival (iDFS); lymphoedema, arm mobility
- Statistical methods
Non-inferiority (HR upper CI <1.271; 5-y iDFS >=85%)
5. Actual results
- Results
5-year iDFS 91.9% (89.9-93.5) without axillary surgery vs 91.7% (90.8-92.6) with SLNB; HR 0.91 (0.73-1.14). Axillary recurrence 1.0% vs 0.3%; death 1.4% vs 2.4%. Less lymphoedema, better arm mobility and less pain without axillary surgery.
- Absolute risks
5-y iDFS difference +0.2 percentage points (recalculated).
- Authors' conclusion
Omission of surgical axillary staging was non-inferior to sentinel-lymph-node biopsy in clinically node-negative T1-T2 breast cancer treated with breast-conserving therapy.
6. Strengths
- Large RCT
- Long follow-up
- Patient-reported harms
7. Weaknesses
- Per-protocol primary analysis
- Mostly small T1 tumours
- All patients still had breast-conserving tumour surgery and radiotherapy
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Open-label by necessity; objective survival outcome.
9. Assessment of the statistical interpretation
HR CI log-symmetric; upper limit 1.14 below the non-inferiority margin (stats/C-SRC-45_insema_refusal.py).
10. Relevance to the specific claim
Supports the part of his criticism that lymph-node surgery can be reduced: in selected early breast cancer even sentinel-node biopsy can be omitted. But this de-escalation comes from surgical oncology trials and all patients had their tumour removed.
11. Independent contrary findings
Tumour removal remains standard (NICE NG101); refusal of surgery associated with higher mortality (I-SRC-107).
12. Transferability to Germany and Europe
Directly applicable (German/Austrian trial).
13. Overall methodological judgement
High-quality trial supporting less axillary surgery in selected patients, not less tumour surgery.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | high |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Applicability to larger tumours, other cancer types.
15. Linked fact checks
- Surgical oncologists do not understand what tumours are: they remove the tumour and 'clean out' the lymph nodes, which he regards as wrong. – Studies with mixed or unclear results