World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Review

Volume 17, Number 3, June 2026, pages 292-309

Omission of Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: Expanding Evidence in Clinically Node-Negative and Neoadjuvant Therapy Responders

↓ **Table 1.** Clinical Trials Evaluating Omission of Axillary Surgery in Clinically Node-Negative Early-Stage Breast Cancer
Trial	Location	Population	Study design	Primary endpoint	Secondary endpoints	Axillary lymph node evaluation	Radiation
SLNB: sentinel lymph node biopsy; QUAD: quadrantectomy with axillary lymph node dissection; QU: quadrantectomy alone; WBR: whole breast radiation; SOUND: Sentinel Node vs Observation After Axillary Ultra-Sound; INSEMA: Intergroup Sentinel Mamma; pBI: partial breast irradiation; BOOG 2013-08: Dutch Breast Cancer Research Group 2013-08; NAUTILUS: No Axillary Surgical Treatment for Lymph Node-Negative Patients after Ultra-Sonography; OMSLNB: Omission of Sentinel Lymph Node Biopsy; MRI: magnetic resonance imaging; pCR: pathologic complete response; US: ultrasonography; BCS: breast conserving surgery; IDFS: invasive disease-free survival; OS: overall survival; DFS: disease-free survival; DDFS: distant disease-free survival; RNI: regional nodal irradiation; RT: radiotherapy; PET/CT: positron emission tomography/computed tomography; QOL: quality of life; 18F-FDG: fluorine-18 fluorodeoxyglucose; cALND: completion axillary lymph node dissection.
INT09/98 [27] (NCT01508546)	Italy	Women < 65 years old with cT1N0 randomized to quadrantectomy without axillary surgery (QU) or quadrantectomy with axillary dissection (QUAD)	Randomized, noninferiority clinical trial	OS	DFS, timing of axillary lymph node metastasis in QU arm	Clinical exam	RT to the breast without intentional inclusion of the axilla, supraclavicular, or internal mammary lymph nodes
SOUND [28] (NCT02167490)	Italy, Spain, Switzerland, Chile	Women of any age with invasive breast cancer ≤ 2 cm, cN0 undergoing BCS and RT (WBR or pBI), randomized 1:1 to SLNB or no axillary surgery	Prospective, multicenter, noninferiority phase 3 randomized clinical trial	DDFS	Cumulative incidence of distant recurrences, cumulative incidence of axillary recurrences, DFS, OS, adjuvant treatment recommendations	Pre-op axillary US	WBR with conventional fractionation, intraoperative boost (ELIOT) followed by hypofractionated course of WBR or pBI
INSEMA [29] (NCT02466737)	Germany, Austria	Women ≥ 18 years old with cT1–T2, cN0 breast cancer undergoing BCS with WBR, randomized 1:4 to undergo omission of axillary surgery or to SLNB, those randomized to SLNB found to be pN1 were randomized 1:1 to cALND or omission of cALND	Prospective, multicenter, noninferiority randomized clinical trial	IDFS	OS, locoregional DFS, ipsilateral axillary recurrence, DDFS, QOL measures, dose distribution in ipsilateral axilla levels I–III during RT	Clinical exam and pre-op axillary US	WBR with conventional fractionation or moderate hypofractionation, without targeting of the axilla, boost RT to the tumor bed recommended
BOOG2013-08 [30] (NCT02271828)	Netherlands	Women ≥ 18 years old with cT1–2N0 breast cancer undergoing BCS with WBR randomized to SLNB or no axillary surgery	Prospective, multicenter, noninferiority randomized clinical trial	RR	DDFS, OS, local recurrence rate, contralateral breast cancer, delayed axillary treatment, adjuvant RT, QOL, morbidity, cost-effectiveness	Clinical exam and pre-op axillary US	WBR
NAUTILUS [31] (NCT04303715)	Korea	Women ≥ 19 years old with cT1–2N0 breast cancer undergoing BCS with WBR, ECOG performance status 0–2, randomized 1:1 to SLNB or no axillary surgery	Prospective, multicenter, noninferiority randomized clinical trial	IDFS	OS, distant metastasis free survival, local recurrence, axillary recurrence, QOL	Clinical exam and pre-op axillary US	WBR for the no-SLNB arm, inclusion of axillary levels I and II are recommended within the tangential field
OMSLNB [33] (NCT05935150)	China	Women 18–70 years old with breast cancers ≤ 3 cm, cN0 undergoing BCS with WBR or mastectomy without axillary surgery, with ECOG performance status 0–1	Prospective, single-arm, noninferiority, phase II, open-label trial	IDFS	Local recurrence, regional recurrence, locoregional recurrence, incidence of lymphedema, QOL	Clinical exam and two or more imaging tests, including axillary US and MRI, PET-CT, or 18F-FDG PET/MRI	WBR (excluding the axilla)
VENUS [32] (NCT05315154)	Brazil	Women ≥ 18 years old with cT1–2N0 breast cancer undergoing BCS or mastectomy, randomized to SLNB or no axillary surgery. Women undergoing neoadjuvant systemic therapy were not excluded.	Prospective, noninferiority, randomized clinical trial	DFS	OS, regional recurrence-free survival, axillary recurrence rate, axillary morbidity, US accuracy, cost effectiveness	Clinical exam and pre-op axillary US	Not specified

↓ Table 1. Clinical Trials Evaluating Omission of Axillary Surgery in Clinically Node-Negative Early-Stage Breast Cancer

Trial

Location

Population

Study design

Primary endpoint

Secondary endpoints

Axillary lymph node evaluation

Radiation

SLNB: sentinel lymph node biopsy; QUAD: quadrantectomy with axillary lymph node dissection; QU: quadrantectomy alone; WBR: whole breast radiation; SOUND: Sentinel Node vs Observation After Axillary Ultra-Sound; INSEMA: Intergroup Sentinel Mamma; pBI: partial breast irradiation; BOOG 2013-08: Dutch Breast Cancer Research Group 2013-08; NAUTILUS: No Axillary Surgical Treatment for Lymph Node-Negative Patients after Ultra-Sonography; OMSLNB: Omission of Sentinel Lymph Node Biopsy; MRI: magnetic resonance imaging; pCR: pathologic complete response; US: ultrasonography; BCS: breast conserving surgery; IDFS: invasive disease-free survival; OS: overall survival; DFS: disease-free survival; DDFS: distant disease-free survival; RNI: regional nodal irradiation; RT: radiotherapy; PET/CT: positron emission tomography/computed tomography; QOL: quality of life; 18F-FDG: fluorine-18 fluorodeoxyglucose; cALND: completion axillary lymph node dissection.

INT09/98 [27] (NCT01508546)

Italy

Women < 65 years old with cT1N0 randomized to quadrantectomy without axillary surgery (QU) or quadrantectomy with axillary dissection (QUAD)

Randomized, noninferiority clinical trial

DFS, timing of axillary lymph node metastasis in QU arm

Clinical exam

RT to the breast without intentional inclusion of the axilla, supraclavicular, or internal mammary lymph nodes

SOUND [28] (NCT02167490)

Italy, Spain, Switzerland, Chile

Women of any age with invasive breast cancer ≤ 2 cm, cN0 undergoing BCS and RT (WBR or pBI), randomized 1:1 to SLNB or no axillary surgery

Prospective, multicenter, noninferiority phase 3 randomized clinical trial

DDFS

Cumulative incidence of distant recurrences, cumulative incidence of axillary recurrences, DFS, OS, adjuvant treatment recommendations

Pre-op axillary US

WBR with conventional fractionation, intraoperative boost (ELIOT) followed by hypofractionated course of WBR or pBI

INSEMA [29] (NCT02466737)

Germany, Austria

Women ≥ 18 years old with cT1–T2, cN0 breast cancer undergoing BCS with WBR, randomized 1:4 to undergo omission of axillary surgery or to SLNB, those randomized to SLNB found to be pN1 were randomized 1:1 to cALND or omission of cALND

Prospective, multicenter, noninferiority randomized clinical trial

IDFS

OS, locoregional DFS, ipsilateral axillary recurrence, DDFS, QOL measures, dose distribution in ipsilateral axilla levels I–III during RT

Clinical exam and pre-op axillary US

WBR with conventional fractionation or moderate hypofractionation, without targeting of the axilla, boost RT to the tumor bed recommended

BOOG2013-08 [30] (NCT02271828)

Netherlands

Women ≥ 18 years old with cT1–2N0 breast cancer undergoing BCS with WBR randomized to SLNB or no axillary surgery

Prospective, multicenter, noninferiority randomized clinical trial

DDFS, OS, local recurrence rate, contralateral breast cancer, delayed axillary treatment, adjuvant RT, QOL, morbidity, cost-effectiveness

Clinical exam and pre-op axillary US

WBR

NAUTILUS [31] (NCT04303715)

Korea

Women ≥ 19 years old with cT1–2N0 breast cancer undergoing BCS with WBR, ECOG performance status 0–2, randomized 1:1 to SLNB or no axillary surgery

Prospective, multicenter, noninferiority randomized clinical trial

IDFS

OS, distant metastasis free survival, local recurrence, axillary recurrence, QOL

Clinical exam and pre-op axillary US

WBR for the no-SLNB arm, inclusion of axillary levels I and II are recommended within the tangential field

OMSLNB [33] (NCT05935150)

China

Women 18–70 years old with breast cancers ≤ 3 cm, cN0 undergoing BCS with WBR or mastectomy without axillary surgery, with ECOG performance status 0–1

Prospective, single-arm, noninferiority, phase II, open-label trial

IDFS

Local recurrence, regional recurrence, locoregional recurrence, incidence of lymphedema, QOL

Clinical exam and two or more imaging tests, including axillary US and MRI, PET-CT, or 18F-FDG PET/MRI

WBR (excluding the axilla)

VENUS [32] (NCT05315154)

Brazil

Women ≥ 18 years old with cT1–2N0 breast cancer undergoing BCS or mastectomy, randomized to SLNB or no axillary surgery. Women undergoing neoadjuvant systemic therapy were not excluded.

Prospective, noninferiority, randomized clinical trial

DFS

OS, regional recurrence-free survival, axillary recurrence rate, axillary morbidity, US accuracy, cost effectiveness

Clinical exam and pre-op axillary US

Not specified

↓ **Table 2.** Results of Clinical Trials Evaluating Omission of Axillary Surgery in Clinically Node-Negative Early-Stage BC
Trial	Follow-up	Population	Mean age (range)	Median clinical tumor size	Lymph node positivity	Recurrence	Survival	Adjuvant therapies	Conclusion
BC: breast cancer; AS: axillary surgery; SLNB: sentinel lymph node biopsy; QUAD: quadrantectomy with axillary lymph node dissection; QU: quadrantectomy alone; WBR: whole breast radiation; SOUND: Sentinel Node vs Observation After Axillary Ultra-Sound; INSEMA: Intergroup Sentinel Mamma; pBI: partial breast irradiation; BOOG 2013-08: Dutch Breast Cancer Research Group 2013-08; US: ultrasonography; BCS: breast conserving surgery; IDFS: invasive disease-free survival; OS: overall survival; DFS: disease-free survival; DDFS: distant disease-free survival; RT: radiotherapy; pre-op: preoperative; cALND: completion axillary lymph node dissection; BCM: breast cancer mortality; ER: estrogen receptor; HR: hormone receptor; RRFS: regional recurrence-free survival.
INT09/98 [27], n = 517, enrollment: 1998–2003	20 years	Women < 65 years old with cT1N0 were randomized to quadrantectomy without axillary surgery (QU) or quadrantectomy with axillary dissection (QUAD)	52.6 years (30–65 years)	1.5 (1.1–1.9) cm	QUAD arm with 28.7%	Local recurrence (QU: 12.2%; QUAD: 12.5%) Axillary recurrence (QU: 10.6%; QUAD: 0.37%) Distant metastases (QU: 17.6%; QUAD: 13.2%)	OS (QU: 76.8%; QUAD: 77.3%; adjusted hazard ratio of QU vs QUAD arm 1.18 for OS; P = 0.326) DFS (QU: 81.5%; QUAD: 86.9%; adjusted hazard ratio of QU vs QUAD arm 1.27 for DFS; P = 0.280) BCM (QU: 14.3%; QUAD: 11%) Statistical analysis via Kaplan-Meier method, compared using log-rank test	Chemotherapy (QU: 35.5%; QUAD: 51.5%)	At 20 years follow-up, no significant difference in OS, BCM, or DFS in patients undergoing vs omitting axillary dissection
SOUND [28], n = 1,405, enrollment: 2012–2017	5 years	Women of any age with invasive BC ≤ 2 cm, cN0 by pre-op axillary US, undergoing BCS and RT (WBR or pBI), randomized 1:1 to SLNB or no axillary surgery	60 years (52–68 years)	1.1 (0.8–1.5) cm	SLNB arm with 13.7%	Local recurrence (SLNB: 1.0%; no AS: 0.9%) Axillary recurrence (SLNB: 0.4%; no AS: 0.7%) Distant metastasis (SLNB: 1.8%; no AS: 2.0%) Cumulative incidence of distant metastasis (SLNB: 2.3%; no AS: 1.9%; Gray P = 0.69) Cumulative incidence of axillary recurrences (SLNB: 0.4%; no AS: 0.4%; Gray P = 0.91)	DDFS (SLNB: 97.7%; no AS: 98.0%; P = 0.67) DFS (SLNB: 94.7%; no AS: 93.9%; P = 0.30) OS (SLNB: 98.2%; no AS: 98.4%; P = 0.72) Statistical analysis via Kaplan-Meier method, compared using log-rank test	Chemotherapy (SLNB: 20.1%; no AS: 17.5%) In HER2+ disease patients receiving trastuzumab (SLNB: 93.8%; no AS: 97.9%) RT (SLNB: 98.0%; no AS: 97.6%) pBI (SLNB: 10.7%; no AS: 10.8%) ET in ER+ BC (SLNB: 97.9%; no AS: 98.9%)	At 5 years follow-up, omission of axillary surgery was noninferior to SLNB for DDFS in postmenopausal women with ER+, HER2– BC who are cN0 with tumors ≤ 2 cm, adjuvant treatments were not significantly different between treatment groups supporting trend of decisions made based on biologic tumor data
INSEMA [29], n = 4,858, enrollment: 2015–2019	5 years	Women >18 years old with cT1–T2, cN0 BC undergoing BCS with WBR, randomized 1:4 to undergo omission of axillary surgery or to SLNB, those randomized to SLNB who were found to be pN1 were randomized 1:1 to cALND or omission of cALND	62 years (24–89 years)	1.1 (0.8–1.6) cm	SLNB arm with 15.0%	Local recurrence (SLNB 1.1%; no AS: 0.8%) Axillary recurrence (SLNB: 0.3%; no AS: 1.0%) Distant metastasis (SLNB: 2.7%; no AS: 2.7%)	5-year IDFS (SLNB: 91.7% (95% CI, 90.8–92.6); no AS: 91.9% (95% CI, 89.9–93.5)) 5-year OS (SLNB: 96.9% (95% CI, 96.3–97.5); no AS: 98.2% (95% CI, 97.1–98.9))	Chemotherapy (SLNB: 12.9%; no AS: 10.4%)	At 6 years follow-up, omission of axillary surgery was noninferior to SLNB for IDFS and suggests omission of SLNB may be reasonable for women ≥ 50 years old with HR+, HER2–, low grade, cT1 BC
BOOG2013-08 [36], n = 1,572, enrollment 2015–2022	5 years	Women ≥ 18 years old with cT1–2N0 BC undergoing BCS with WBR randomized to SLNB or no axillary surgery	61 years	Not yet reported	SLNB arm with 13.7%	Local recurrence (SLNB: 15.3%; no AS: 9.1%) Regional recurrence (SLNB: 5.1%; no AS: 9.1%) Distant metastasis (SLNB: 23.7%; no AS: 29.5%)	RRFS (SLNB: 96.6% (95% CI, 95.2–98.0); no AS: 94.2% (95% CI, 92.4–96.0)) DDFS (SLNB: 96.0% (95% CI, 94.4–97.6); no AS: 92.9% (95% CI 90.0–94.9); absolute difference of 3.3%)	Chemotherapy (SLNB: 13.0%; no AS: 11.3%) Targeted therapy (SLNB: 5.9%; no AS: 4.4%) Endocrine therapy (SLNB: 44.8%; no AS: 43.1%)	At median 5 years follow-up, omission of axillary surgery was noninferior to SLNB for RRFS and suggests omission of SLNB may be reasonable in women ≥ 50 years old with HR+, HER2–, grade 1–2, cT1 BC

↓ Table 2. Results of Clinical Trials Evaluating Omission of Axillary Surgery in Clinically Node-Negative Early-Stage BC

Trial

Follow-up

Population

Mean age (range)

Median clinical tumor size

Lymph node positivity

Recurrence

Survival

Adjuvant therapies

Conclusion

BC: breast cancer; AS: axillary surgery; SLNB: sentinel lymph node biopsy; QUAD: quadrantectomy with axillary lymph node dissection; QU: quadrantectomy alone; WBR: whole breast radiation; SOUND: Sentinel Node vs Observation After Axillary Ultra-Sound; INSEMA: Intergroup Sentinel Mamma; pBI: partial breast irradiation; BOOG 2013-08: Dutch Breast Cancer Research Group 2013-08; US: ultrasonography; BCS: breast conserving surgery; IDFS: invasive disease-free survival; OS: overall survival; DFS: disease-free survival; DDFS: distant disease-free survival; RT: radiotherapy; pre-op: preoperative; cALND: completion axillary lymph node dissection; BCM: breast cancer mortality; ER: estrogen receptor; HR: hormone receptor; RRFS: regional recurrence-free survival.

INT09/98 [27], n = 517, enrollment: 1998–2003

20 years

Women < 65 years old with cT1N0 were randomized to quadrantectomy without axillary surgery (QU) or quadrantectomy with axillary dissection (QUAD)

52.6 years (30–65 years)

1.5 (1.1–1.9) cm

QUAD arm with 28.7%

Local recurrence (QU: 12.2%; QUAD: 12.5%)
Axillary recurrence (QU: 10.6%; QUAD: 0.37%)
Distant metastases (QU: 17.6%; QUAD: 13.2%)

OS (QU: 76.8%; QUAD: 77.3%; adjusted hazard ratio of QU vs QUAD arm 1.18 for OS; P = 0.326)
DFS (QU: 81.5%; QUAD: 86.9%; adjusted hazard ratio of QU vs QUAD arm 1.27 for DFS; P = 0.280)
BCM (QU: 14.3%; QUAD: 11%)
Statistical analysis via Kaplan-Meier method, compared using log-rank test

Chemotherapy (QU: 35.5%; QUAD: 51.5%)

At 20 years follow-up, no significant difference in OS, BCM, or DFS in patients undergoing vs omitting axillary dissection

SOUND [28], n = 1,405, enrollment: 2012–2017

5 years

Women of any age with invasive BC ≤ 2 cm, cN0 by pre-op axillary US, undergoing BCS and RT (WBR or pBI), randomized 1:1 to SLNB or no axillary surgery

60 years (52–68 years)

1.1 (0.8–1.5) cm

SLNB arm with 13.7%

Local recurrence (SLNB: 1.0%; no AS: 0.9%)
Axillary recurrence (SLNB: 0.4%; no AS: 0.7%)
Distant metastasis (SLNB: 1.8%; no AS: 2.0%)
Cumulative incidence of distant metastasis (SLNB: 2.3%; no AS: 1.9%; Gray P = 0.69)
Cumulative incidence of axillary recurrences (SLNB: 0.4%; no AS: 0.4%; Gray P = 0.91)

DDFS (SLNB: 97.7%; no AS: 98.0%; P = 0.67)
DFS (SLNB: 94.7%; no AS: 93.9%; P = 0.30)
OS (SLNB: 98.2%; no AS: 98.4%; P = 0.72)
Statistical analysis via Kaplan-Meier method, compared using log-rank test

Chemotherapy (SLNB: 20.1%; no AS: 17.5%)
In HER2+ disease patients receiving trastuzumab (SLNB: 93.8%; no AS: 97.9%)
RT (SLNB: 98.0%; no AS: 97.6%)
pBI (SLNB: 10.7%; no AS: 10.8%)
ET in ER+ BC (SLNB: 97.9%; no AS: 98.9%)

At 5 years follow-up, omission of axillary surgery was noninferior to SLNB for DDFS in postmenopausal women with ER+, HER2– BC who are cN0 with tumors ≤ 2 cm, adjuvant treatments were not significantly different between treatment groups supporting trend of decisions made based on biologic tumor data

INSEMA [29], n = 4,858, enrollment: 2015–2019

5 years

Women >18 years old with cT1–T2, cN0 BC undergoing BCS with WBR, randomized 1:4 to undergo omission of axillary surgery or to SLNB, those randomized to SLNB who were found to be pN1 were randomized 1:1 to cALND or omission of cALND

62 years (24–89 years)

1.1 (0.8–1.6) cm

SLNB arm with 15.0%

Local recurrence (SLNB 1.1%; no AS: 0.8%)
Axillary recurrence (SLNB: 0.3%; no AS: 1.0%)
Distant metastasis (SLNB: 2.7%; no AS: 2.7%)

5-year IDFS (SLNB: 91.7% (95% CI, 90.8–92.6); no AS: 91.9% (95% CI, 89.9–93.5))
5-year OS (SLNB: 96.9% (95% CI, 96.3–97.5); no AS: 98.2% (95% CI, 97.1–98.9))

Chemotherapy (SLNB: 12.9%; no AS: 10.4%)

At 6 years follow-up, omission of axillary surgery was noninferior to SLNB for IDFS and suggests omission of SLNB may be reasonable for women ≥ 50 years old with HR+, HER2–, low grade, cT1 BC

BOOG2013-08 [36], n = 1,572, enrollment 2015–2022

5 years

Women ≥ 18 years old with cT1–2N0 BC undergoing BCS with WBR randomized to SLNB or no axillary surgery

61 years

Not yet reported

SLNB arm with 13.7%

Local recurrence (SLNB: 15.3%; no AS: 9.1%)
Regional recurrence (SLNB: 5.1%; no AS: 9.1%)
Distant metastasis (SLNB: 23.7%; no AS: 29.5%)

RRFS (SLNB: 96.6% (95% CI, 95.2–98.0); no AS: 94.2% (95% CI, 92.4–96.0))
DDFS (SLNB: 96.0% (95% CI, 94.4–97.6); no AS: 92.9% (95% CI 90.0–94.9); absolute difference of 3.3%)

Chemotherapy (SLNB: 13.0%; no AS: 11.3%)
Targeted therapy (SLNB: 5.9%; no AS: 4.4%)
Endocrine therapy (SLNB: 44.8%; no AS: 43.1%)

At median 5 years follow-up, omission of axillary surgery was noninferior to SLNB for RRFS and suggests omission of SLNB may be reasonable in women ≥ 50 years old with HR+, HER2–, grade 1–2, cT1 BC

↓ **Table 3.** Clinical Trials Evaluating Omission of Sentinel Lymph Node Biopsy After Neoadjuvant Systemic Therapy
Trial	Location	Study design	Population	Planned enrollment	Primary endpoint	Secondary endpoints	Axillary lymph node evaluation	Radiation
SLNB: sentinel lymph node biopsy; HER2: human epidermal growth factor receptor 2; EUBREAST: European Breast Cancer Research Association of Surgical Trialists; ASICS: Avoiding Sentinel lymph node biopsy In select Clinical node negative breast cancer patients after neoadjuvant Systemic therapy; ASLAN: Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy; Neo-NAUTILUS: No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy; TNBC: triple-negative breast cancer; MRI: magnetic resonance imaging; pCR: pathologic complete response; rCR: radiologic complete response; US: ultrasonography; BCS: breast conserving surgery; IDFS: invasive disease-free survival; OS: overall survival; DFS: disease-free survival; RFS: recurrence-free survival; RNI: regional nodal irradiation; ARFS: axillary recurrence-free survival; NAST: neoadjuvant systemic therapy; RT: radiotherapy; PET/CT: positron emission tomography/computed tomography; QOL: quality of life; WBR: whole breast radiation; pre-op: preoperative; BCSS: breast cancer-specific survival.
EUBREAST-01 [56] (NCT04101851)	Germany	Multicenter, prospective, single-arm trial	Women ≥ 18 years old with cT1c–3, N0, M0 TNBC or HER2+ invasive breast cancer who received NAST with rCR (by mammogram and axillary US, or MRI), undergoing BCS with WBR, will be assigned to not undergo SLNB once a pCR was confirmed in the breast (ypT0).	N = 267	3-year axillary recurrence free survival	5-year IDFS, OS, locoregional disease-free survival, ARFS, ipsilateral axillary recurrence rate, diagnostic accuracy of imaging methods	Clinical exam and pre-op axillary US prior to NAST and surgery	WBR with boost to the tumor bed, hypofractionated regimen is allowed, extension of radiation field to high tangents is not recommended
ASICS [57] (NCT04225858)	Netherlands	Prospective noninferiority cohort, single-arm trial	Women ≥ 18 years old with cT1–3, N0, M0 TNBC or HER2+ invasive breast cancer who received NAST with rCR (by MRI), will be assigned to omit SLNB.	N = 340	5-year axillary recurrence	5-year RFS, OS, DFS, and QOL outcomes	Pre-op axillary US and FDG-PET/CT	Not specified
ASLAN [58] (NCT04993625)	Korea	Multicenter, prospective, single-arm trial	Women 20–69 years old with cT1–3, N0–1, M0 HER2+ or TNBC breast cancer, expected to achieve breast pCR based on imaging (breast mammogram, US, and MRI) and physical exam following NAST. Patients will undergo BCS with adjuvant RT and omission of SLNB.	N = 178	5-year recurrence free survival	5-year ipsilateral breast tumor recurrence and ipsilateral axillary recurrence intervals, distant metastasis free survival, BCSS, OS, contralateral breast cancer free survival, re-operation rates, adverse events, and QOL	Breast mammogram, US, MRI	WBR (conventional or hypofractionated) with RNI including axillary level I and II
Neo-NAUTILUS [60] (NCT06704945)	Korea	Multicenter, prospective, randomized, controlled, phase III, noninferiority trial	Women ≥ 20 years old with cT1–3, N0, M0 breast cancer of any subtype, or select cT1-3, N1, M0 breast cancer that is HER2+ or TNBC with tumor response > 30% on MRI, undergoing BCS with adjuvant RT, randomized 1:1 to SLNB or no SLNB, were stratified by clinical nodal status and tumor subtype.	N = 464	5-year invasive disease-free survival	5-year OS, distant metastasis free survival, ipsilateral axillary recurrence, locoregional recurrence, rate of residual nodal disease, QOL outcomes	Post-NAST axillary US, breast MRI if initially cN1	WBR (conventional or hypofractionated) included either standard tangents or WBR with level I axillary coverage if cN0 in omission of SLNB arm; if cN1 WBR with standard tangents, level I axillary coverage, high tangents, or RNI

↓ Table 3. Clinical Trials Evaluating Omission of Sentinel Lymph Node Biopsy After Neoadjuvant Systemic Therapy

Trial

Location

Study design

Population

Planned enrollment

Primary endpoint

Secondary endpoints

Axillary lymph node evaluation

Radiation

SLNB: sentinel lymph node biopsy; HER2: human epidermal growth factor receptor 2; EUBREAST: European Breast Cancer Research Association of Surgical Trialists; ASICS: Avoiding Sentinel lymph node biopsy In select Clinical node negative breast cancer patients after neoadjuvant Systemic therapy; ASLAN: Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy; Neo-NAUTILUS: No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy; TNBC: triple-negative breast cancer; MRI: magnetic resonance imaging; pCR: pathologic complete response; rCR: radiologic complete response; US: ultrasonography; BCS: breast conserving surgery; IDFS: invasive disease-free survival; OS: overall survival; DFS: disease-free survival; RFS: recurrence-free survival; RNI: regional nodal irradiation; ARFS: axillary recurrence-free survival; NAST: neoadjuvant systemic therapy; RT: radiotherapy; PET/CT: positron emission tomography/computed tomography; QOL: quality of life; WBR: whole breast radiation; pre-op: preoperative; BCSS: breast cancer-specific survival.

EUBREAST-01 [56] (NCT04101851)

Germany

Multicenter, prospective, single-arm trial

Women ≥ 18 years old with cT1c–3, N0, M0 TNBC or HER2+ invasive breast cancer who received NAST with rCR (by mammogram and axillary US, or MRI), undergoing BCS with WBR, will be assigned to not undergo SLNB once a pCR was confirmed in the breast (ypT0).

N = 267

3-year axillary recurrence free survival

5-year IDFS, OS, locoregional disease-free survival, ARFS, ipsilateral axillary recurrence rate, diagnostic accuracy of imaging methods

Clinical exam and pre-op axillary US prior to NAST and surgery

WBR with boost to the tumor bed, hypofractionated regimen is allowed, extension of radiation field to high tangents is not recommended

ASICS [57] (NCT04225858)

Netherlands

Prospective noninferiority cohort, single-arm trial

Women ≥ 18 years old with cT1–3, N0, M0 TNBC or HER2+ invasive breast cancer who received NAST with rCR (by MRI), will be assigned to omit SLNB.

N = 340

5-year axillary recurrence

5-year RFS, OS, DFS, and QOL outcomes

Pre-op axillary US and FDG-PET/CT

Not specified

ASLAN [58] (NCT04993625)

Korea

Multicenter, prospective, single-arm trial

Women 20–69 years old with cT1–3, N0–1, M0 HER2+ or TNBC breast cancer, expected to achieve breast pCR based on imaging (breast mammogram, US, and MRI) and physical exam following NAST. Patients will undergo BCS with adjuvant RT and omission of SLNB.

N = 178

5-year recurrence free survival

5-year ipsilateral breast tumor recurrence and ipsilateral axillary recurrence intervals, distant metastasis free survival, BCSS, OS, contralateral breast cancer free survival, re-operation rates, adverse events, and QOL

Breast mammogram, US, MRI

WBR (conventional or hypofractionated) with RNI including axillary level I and II

Neo-NAUTILUS [60] (NCT06704945)

Korea

Multicenter, prospective, randomized, controlled, phase III, noninferiority trial

Women ≥ 20 years old with cT1–3, N0, M0 breast cancer of any subtype, or select cT1-3, N1, M0 breast cancer that is HER2+ or TNBC with tumor response > 30% on MRI, undergoing BCS with adjuvant RT, randomized 1:1 to SLNB or no SLNB, were stratified by clinical nodal status and tumor subtype.

N = 464

5-year invasive disease-free survival

5-year OS, distant metastasis free survival, ipsilateral axillary recurrence, locoregional recurrence, rate of residual nodal disease, QOL outcomes

Post-NAST axillary US, breast MRI if initially cN1

WBR (conventional or hypofractionated) included either standard tangents or WBR with level I axillary coverage if cN0 in omission of SLNB arm; if cN1 WBR with standard tangents, level I axillary coverage, high tangents, or RNI

↓ **Table 4.** Key Clinical Takeaways of Consideration of Omission of Sentinel Lymph Node Biopsy After Neoadjuvant Systemic Therapy
SLNB: sentinel lymph node biopsy; HER2: human epidermal growth factor receptor 2; EUBREAST: European Breast Cancer Research Association of Surgical Trialists; ASICS: Avoiding Sentinel lymph node biopsy In select Clinical node negative breast cancer patients after neoadjuvant Systemic therapy; ASLAN: Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy; Neo-NAUTILUS: No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy.
Investigational nature of SLNB omission after neoadjuvant therapy
Omission of SLNB following NAST remains investigational and is not yet standard of care.
Patient populations with the most promising data
Patients with HER2- positive and triple-negative breast cancer who achieve breast pathologic complete response demonstrate extremely low rates of residual nodal disease [47–49, 51]
In clinically node-negative patients, breast pathologic complete response is highly predictive of axillary pathologic complete response [47, 49, 51, 52]
Risk of residual nodal disease
Reported rates of residual nodal disease in clinically node-negative HER2-positive and triple-negative patients with pathologic complete response are approximately 1–2%, below accepted false-negative thresholds for SLNB [48, 50]
The likelihood of nodal involvement is higher in patients with:
Residual breast disease [47, 48]
Hormone receptor-positive/HER2-negative tumors [48, 49, 55]
Initial node-positive disease [47, 49]
Ongoing clinical trials
Multiple prospective trials are evaluating omission of SLNB in this setting, including:
EUBREAST-01 [56]
ASICS [57]
ASLAN [58]
Neo-NAUTILUS [60]
Clinical implications
If validated, omission of SLNB in carefully selected patients may:
Reduce surgical morbidity (lymphedema, pain, functional impairment)
Further advance de-escalation of axillary surgery
Support more personalized, response-adapted treatment strategies

↓ Table 4. Key Clinical Takeaways of Consideration of Omission of Sentinel Lymph Node Biopsy After Neoadjuvant Systemic Therapy

Investigational nature of SLNB omission after neoadjuvant therapy

Omission of SLNB following NAST remains investigational and is not yet standard of care.

Patient populations with the most promising data

Patients with HER2- positive and triple-negative breast cancer who achieve breast pathologic complete response demonstrate extremely low rates of residual nodal disease [47–49, 51]

In clinically node-negative patients, breast pathologic complete response is highly predictive of axillary pathologic complete response [47, 49, 51, 52]

Risk of residual nodal disease

Reported rates of residual nodal disease in clinically node-negative HER2-positive and triple-negative patients with pathologic complete response are approximately 1–2%, below accepted false-negative thresholds for SLNB [48, 50]

The likelihood of nodal involvement is higher in patients with:

Residual breast disease [47, 48]

Hormone receptor-positive/HER2-negative tumors [48, 49, 55]

Initial node-positive disease [47, 49]

Ongoing clinical trials

Multiple prospective trials are evaluating omission of SLNB in this setting, including:

EUBREAST-01 [56]

ASICS [57]

ASLAN [58]

Neo-NAUTILUS [60]

Clinical implications

If validated, omission of SLNB in carefully selected patients may:

Reduce surgical morbidity (lymphedema, pain, functional impairment)

Further advance de-escalation of axillary surgery

Support more personalized, response-adapted treatment strategies