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Evidence summaries

Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer

The incidence of axillary metastases in patients with negative sentinel node biopsy appears to be low. Level of evidence: "B"

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 3 4 5 6 7 8 9 10 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 11, 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 12 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 [Abstract]13 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 T1).

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 T2).

Sentinel lymph node biopsy (SLNB) versus ALND: There was similar overall survival (table T3).

No axillary surgery compared with full axillary surgery (ALND)

OutcomesRelative effect(95% CI)Assumed risk - Control - Full axillary surgeryCorresponding risk - Intervention - No axillary surgery (95% CI)No of participants(studies) Quality of evidence
All-cause mortalityat 5 yearsHR 1.06 (0.96 to 1.17)92% overall survival92% overall survival (91% to 93%)3 849(10) Moderate
Locoregional recurrence at 5 yearsHR 2.35 (1.91 to 2.89)86% locoregional recurrence-free survival71% locoregional recurrence-free survival (66% to 76%)20 863(5) Moderate
Lymphoedema: Increase in arm circumference Follow-up: 1 or more yearsOR 0.31 (0.23 to 0.43)236 per 100087 per 1000(66 to 117)1 714(4) Low

Axillary sampling compared with full axillary surgery (ALND)

OutcomesRelative effect(95% CI)Assumed risk - Control - Full axillary surgeryCorresponding risk - Intervention - Axillary sampling (95% CI)No of participants(studies) Quality of evidence
All-cause mortality at 5 yearsHR 0.94 (0.73 to 1.21)82% overall survival83% overall survival (79% to 87%)967(3) Low
Local recurrence at 5 yearsHR 1.41 (0.94 to 2.12)85% local recurrence-free survival80% local recurrence free survival (71% to 86%)1 404(3) Low

Sentinel node biopsy (SLNB) compared with full axillary surgery (ALND)

OutcomesRelative effect(95% CI)Assumed risk - Control - Full axillary surgeryCorresponding risk - Intervention - Sentinel node biopsy (95% CI)No of participants(studies) Quality of evidence
All-cause mortality at 5 yearsHR 1.05 (0.89 to 1.25)96% overall survival96% overall survival (95% to 96%)6 352(3) Moderate
Lymphoedema (subjective): Follow-up: 1 yearOR 0.33 (0.15 to 0.86)132 per 100048 per 1000(22 to 115)815(3) Low
Subjective arm movement impairmentFollow-up: 1 yearOR 0.38 (0.22 to 0.67)100 per 100040 per 1000(24 to 69)877(2) Very low

ASCO Guideline 14 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 HASH(0x2fd57c0)50 years of age and with negative findings on preoperative axillary ultrasound for grade 1-2, small (HASH(0x2fd5bc8)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 HASH(0x2fd5bc8)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.

    References

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    • 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 study. Eur J Surg Oncol 2005 Apr;31(3):221-5. [PubMed]
    • 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 analysis of 150 patients after SLN biopsy. Ann Surg 2005 Jan;241(1):152-8. [PubMed]
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    • 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 analysis. J Surg Oncol 2004 Oct 1;88(1):4-7; discussion 7-8. [PubMed]
    • 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 cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection. Eur J Cancer 2005 Jan;41(2):231-7. [PubMed]
    • 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 dissection: a study on 479 breast cancer patients. Eur J Surg Oncol 2005 Sep;31(7):715-20. [PubMed]
    • 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: SenSzi (GBG80) Trial. J Clin Oncol 2019;37(17):1490-1498. [PubMed]
    • 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 cancer at diagnosis? An updated meta-analysis involving 3,398 patients. Am J Surg 2016;212(5):969-981. [PubMed]
    • Bromham N, Schmidt-Hansen M, Astin M, et al. Axillary treatment for operable primary breast cancer. Cochrane Database Syst Rev 2017;1(1):CD004561. [PubMed]
    • 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):17,20-1741. [PubMed]

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