Comment: The quality of evidence is downgraded by imprecise results (few events in randomized trials). The skill of the operator appears to influence the sensitivity of sentinel node biopsy in detecting axillary metastases.
According to 8 observational studies «Blanchard DK, Donohue JH, Reynolds C, Grant CS. Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer. Arch Surg 2003 May;138(5):4»1 «Kokke MC, Jannink I, Barneveld PC, van der Linden JC, Gelderman WA, Wissing JC, Bosscha K. Incidence of axillary recurrence in 113 sentinel node negative breast cancer patients: a 3-year follow-up stu»2 «Langer I, Marti WR, Guller U, Moch H, Harder F, Oertli D, Zuber M. Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analys»3 «Naik AM, Fey J, Gemignani M, Heerdt A, Montgomery L, Petrek J, Port E, Sacchini V, Sclafani L, VanZee K, Wagman R, Borgen PI, Cody HS 3rd. The risk of axillary relapse after sentinel lymph node biopsy»4 «Reitsamer R, Peintinger F, Prokop E, Rettenbacher L, Menzel C. 200 Sentinel lymph node biopsies without axillary lymph node dissection -- no axillary recurrences after a 3-year follow-up. Br J Cancer »5 «Torrenga H, Fabry H, van der Sijp JR, van Diest PJ, Pijpers R, Meijer S. Omitting axillary lymph node dissection in sentinel node negative breast cancer patients is safe: a long term follow-up analysi»6 «Veronesi U, Galimberti V, Mariani L, Gatti G, Paganelli G, Viale G, Zurrida S, Veronesi P, Intra M, Gennari R, Rita Vento A, Luini A, Tullii M, Bassani G, Rotmensz N. Sentinel node biopsy in breast ca»7 «Zavagno G, Carcoforo P, Franchini Z, Renier M, Barutta L, De Salvo GL, Maravegias K, Capitanio G, Nitti D, Lise M. Axillary recurrence after negative sentinel lymph node biopsy without axillary dissec»8 with a median follow-up of 3 – 5 years, the rate of axillary recurrence was about 0.3%.
In a prospective, multicenter, randomized phase III trial «Kuemmel S, Holtschmidt J, Gerber B et al. Prospective, Multicenter, Randomized Phase III Trial Evaluating the Impact of Lymphoscintigraphy as Part of Sentinel Node Biopsy in Early Breast Cancer: SenSz»9, patients with cN0 early breast cancer or extensive/high-grade ductal carcinoma in situ planned for standard radioactive-labeled colloid lymphoscintigraphy (LSG) with subsequent SLN biopsy (SNLB) were randomly assigned 1:1 to receive SLNB either with knowledge of the LSG findings or without. Modified intention-to-treat analysis (n = 1163) showed a mean number of histologically detected SLNs of 2.21 with LSG and 2.26 without LSG (difference 0.05; stratified 95% CI -0.18 to infinity), thus establishing noninferiority of omitting preoperative LSG. Secondary end points displayed no statistically significant differences.
A meta-analysis «El Hage Chehade H, Headon H, El Tokhy O et al. Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast »10 assessing the use of SLNB following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes included 3398 patients. The pooled estimate of the FNR was 13% and that of the identification rate was 91%. The adjusted axillary pathological complete response rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased axillary pathological complete response rate when compared to N2 or N3 disease (P = .06).
A Cochrane review «Axillary treatment for operable primary breast cancer»1 «Bromham N, Schmidt-Hansen M, Astin M, et al. Axillary treatment for operable primary breast cancer. Cochrane Database Syst Rev 2017;1(1):CD004561. »11 included 26 studies with operable primary breast cancer. No axillary surgery versus axillary lymph node dissection (ALND): There were no important differences between overall survival although no axillary surgery increased the risk of locoregional recurrence but also decreased the risk of lymphoedema (table «No axillary surgery compared with full axillary surgery (ALND)»1).
Axillary sampling versus ALND: There was similar effectiveness in terms of overall survival but it was unclear whether axillary sampling led to increased risk of local recurrence (table «Axillary sampling compared with full axillary surgery (ALND)»2).
Sentinel lymph node biopsy (SLNB) versus ALND: There was similar overall survival (table «Sentinel node biopsy (SLNB) compared with full axillary surgery (ALND)»3).
| Outcomes | Relative effect (95% CI) | Assumed risk - Control - Full axillary surgery | Corresponding risk - Intervention - No axillary surgery (95% CI) | No of participants (studies) Quality of evidence |
|---|---|---|---|---|
| All-cause mortality at 5 years | HR 1.06 (0.96 to 1.17) | 92% overall survival | 92% overall survival (91% to 93%) | 3 849 (10) Moderate |
| Locoregional recurrence at 5 years | HR 2.35 (1.91 to 2.89) | 86% locoregional recurrence-free survival | 71% locoregional recurrence-free survival (66% to 76%) | 20 863 (5) Moderate |
| Lymphoedema: Increase in arm circumference Follow-up: 1 or more years | OR 0.31 (0.23 to 0.43) | 236 per 1000 | 87 per 1000 (66 to 117) | 1 714 (4) Low |
| Outcomes | Relative effect (95% CI) | Assumed risk - Control - Full axillary surgery | Corresponding risk - Intervention - Axillary sampling (95% CI) | No of participants (studies) Quality of evidence |
|---|---|---|---|---|
| All-cause mortality at 5 years | HR 0.94 (0.73 to 1.21) | 82% overall survival | 83% overall survival (79% to 87%) | 967 (3) Low |
| Local recurrence at 5 years | HR 1.41 (0.94 to 2.12) | 85% local recurrence-free survival | 80% local recurrence free survival (71% to 86%) | 1 404 (3) Low |
| Outcomes | Relative effect (95% CI) | Assumed risk - Control - Full axillary surgery | Corresponding risk - Intervention - Sentinel node biopsy (95% CI) | No of participants (studies) Quality of evidence |
|---|---|---|---|---|
| All-cause mortality at 5 years | HR 1.05 (0.89 to 1.25) | 96% overall survival | 96% overall survival (95% to 96%) | 6 352 (3) Moderate |
| Lymphoedema (subjective): Follow-up: 1 year | OR 0.33 (0.15 to 0.86) | 132 per 1000 | 48 per 1000 (22 to 115) | 815 (3) Low |
| Subjective arm movement impairment Follow-up: 1 year | OR 0.38 (0.22 to 0.67) | 100 per 1000 | 40 per 1000 (24 to 69) | 877 (2) Very low |
ASCO Guideline «Park KU, Somerfield MR, Anne N, et al. Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update. J Clin Oncol 2025;43(14):1720-1741. »12 included 11 randomized clinical trials, 8 meta-analyses and/or systematic reviews, and 1 prospective cohort study. The panel did not recommend routine SLNB in select patients who are postmenopausal and ≥50 years of age and with negative findings on preoperative axillary ultrasound for grade 1-2, small (≤2 cm), hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer and who undergo breast-conserving therapy. Clinicians may offer postmastectomy radiation (RT) with regional nodal irradiation (RNI) and omit axillary lymph node dissection (ALND) in patients with clinically node-negative invasive breast cancer ≤5 cm who receive mastectomy and have one to two positive sentinel nodes. Clinicians may offer SLNB in patients who have cT3-T4c or multicentric tumors (clinically node-negative) or ductal carcinoma in situ treated with mastectomy, and in patients who are obese, male, or pregnant, or who have had prior breast or axillary surgery. Clinicians should not recommend ALND for patients with early-stage breast cancer who do not have nodal metastases, and clinicians should not recommend ALND for patients with early-stage breast cancer who have one or two sentinel lymph node metastases and will receive breast-conserving surgery and whole-breast RT with or without RNI.