Evaluating the role of sentinel lymph node biopsy in cT1–2N0M0 breast cancer: a SEER-based study

Abstract

Background

Axillary lymph node staging is vital in breast cancer (BC) management. Sentinel lymph node biopsy (SLNB) reduces complications compared to axillary lymph node dissection (ALND). Recent trials suggest omitting SLNB may be feasible for early-stage patients. This study uses the Surveillance, Epidemiology, and End Results (SEER) database to validate these findings for cT1–2N0M0 patients and explores the relationship between tumor T staging and SLNB.

Methods

We selected BC patients with cT1–2N0M0 stage who underwent breast-conserving surgery (BCS) or BCS + SLNB from the SEER database based on the inclusion and exclusion criteria. Propensity score matching (PSM) was used to balance baseline differences between the two groups. Cox regression analysis was performed to identify independent risk factors for these patients, and Kaplan-Meier (KM) analysis was used to assess survival differences in overall survival (OS) and breast cancer-specific survival (BCSS) between the BCS and BCS + SLNB groups.

Results

This study included 1,470 BC patients, with 215 undergoing BCS and 1,255 undergoing BCS + SLNB. The BCS group had less aggressive tumors and was older on average. Cox regression analysis of patients’ OS and BCSS showed that SLNB was not an independent risk factor for patients. Before PSM, SLNB was associated with improved OS in patients; however, after PSM, this statistical difference disappeared. Subgroup analysis by T staging also indicated no impact of SLNB on OS or BCSS, supporting the feasibility of omitting SLNB for clinically node-negative (cN0) patients.

Conclusions

This study, using the SEER database, found that SLNB did not impact the prognosis of cT1–2N0M0 BC patients, regardless of T stage. This supports previous findings that these patients may avoid axillary surgery without compromising outcomes.

Highlight box.

Key findings

• This study confirms that for early-stage breast cancer (BC) patients with T1/T2 tumors and clinically node-negative (cN0) status, axillary surgery, including sentinel lymph node biopsy (SLNB), can be safely omitted without compromising survival outcomes. Prior studies, such as the ACOSOG Z0011, SOUND, and INSEMA trials, support this conclusion, showing that omitting SLNB does not negatively impact overall survival (OS) or disease-free survival (DFS) in suitable patients.

What is known and what is new?

• It is well-established that SLNB is essential for staging in patients with axillary involvement. However, recent evidence suggests SLNB may not be necessary for early-stage patients with small tumors and no clinical lymph node involvement.

• This manuscript provides additional validation through Surveillance, Epidemiology, and End Results (SEER) dataset analysis, reinforcing the safety and efficacy of omitting SLNB for certain low-risk groups.

What is the implication, and what should change now?

• This study challenges current clinical practices, suggesting that unnecessary SLNB can be avoided in selected early-stage BC patients, reducing surgical risks. Clinical guidelines should incorporate these findings, and further research is needed to explore omitting SLNB in higher-risk groups, considering tumor size and patient characteristics in personalized treatment plans.

Introduction

Axillary lymph node staging is a cornerstone in the surgical management of breast cancer (BC), traditionally serving as a critical method for assessing tumor metastasis and determining prognosis (1,2). Historically, axillary lymph node dissection (ALND) has been the standard treatment, involving the removal of lymph nodes from the axilla to evaluate and control local cancer spread (3,4). However, ALND is associated with significant complications such as lymphedema, upper limb numbness, axillary web syndrome, and reduced arm mobility, all of which can severely impact a patient’s quality of life (5-7).

To mitigate these issues, sentinel lymph node biopsy (SLNB) has emerged as a minimally invasive alternative. SLNB evaluates a small number of lymph nodes to detect cancer spread, offering comparable information on axillary metastasis with less trauma. This approach, particularly in early-stage BC patients, reduces surgical risks and complications while maintaining therapeutic efficacy (6,8). Notably, SLNB has been shown to result in favorable clinical outcomes and better patient tolerance. The ACOSOG Z0011 trial (2005–2015) compared 10-year overall survival (OS) rates between SLNB alone and ALND in T1 and T2 BC patients with no clinical evidence of axillary lymph node metastasis. The study found a 10-year OS rate of 86.3% in the SLNB group compared to 83.6% in the ALND group, with no significant difference in regional recurrence between the groups (9). Furthermore, both the IBCSG 23-01 and AMAROS trials support de-escalation of axillary surgery. IBCSG 23-01 confirmed that ALND can be safely omitted in patients with T1–2 BC and sentinel lymph node micrometastases, whereas AMAROS demonstrated that axillary radiotherapy is a viable alternative to ALND in those with SLN micrometastases, significantly reducing lymphedema risk (10-12). This result suggests that SLNB alone provides comparable long-term survival, challenging the necessity of routine ALND, even for patients with 1–2 positive sentinel lymph nodes. However, as SLNB is a diagnostic procedure rather than a direct treatment, a new question arises: does omitting SLNB in this population impact their prognosis? The CALGB 9343 trial studied radiotherapy omission after lumpectomy in elderly (≥70 years) early BC patients. Notably, two-thirds skipped axillary staging, indirectly supporting SLNB omission in low-risk cases (13). Recent studies, such as the SOUND and INSEMA trials, provide important insights. The SOUND trial (2023) found that observation following axillary ultrasound produced similar prognostic outcomes to traditional SLNB in early-stage BC patients. Specifically, for those with small tumors and no axillary metastasis on ultrasound, axillary surgery could be avoided (14). Similarly, preliminary results from the INSEMA trial suggest that omitting axillary surgery in clinically node-negative, T1 or T2 invasive BC is noninferior to SLNB after a median follow-up of 6 years (15). Furthermore, similar ongoing trials (e.g., BOOG 2013-08, OMSLNB) are currently investigating this approach (16-18).

The growing trend toward de-escalating axillary surgery in BC is gaining momentum. However, it is important to note that while both T1 and T2 patients were included in the SOUND and INSEMA trials, the majority of participants were T1 patients (SOUND: 677/708; INSEMA: 4346/5502). Moreover, few studies have independently validated these results. Thus, in this study, we aim to utilize the Surveillance, Epidemiology, and End Results (SEER) database, applying strict inclusion criteria to select cT1–2N0M0 patients. We validate the findings of the aforementioned studies and perform additional analysis based on tumor T staging to assess the reliability of omitting SLNB in this patient population. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-171/rc).

Methods

Study population

The SEER database, established by the U.S. National Cancer Institute (NCI), is a comprehensive cancer epidemiology repository. It represents approximately 30% of the U.S. population, ensuring broad generalizability. The database provides high-quality data on a wide range of cancer types, including detailed clinical and follow-up information (19). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Our inclusion criteria were as follows: (I) adult women aged over 18 years; (II) patients diagnosed between 2016 and 2017, as the SEER database distinguishes clinical and pathological staging only under the entry ‘Derived.SEER.Combined.TNM..2016.2017’; (III) BC as the first primary tumor; (IV) patients classified as c1/c1A/c1B/c1C/c1MI/c2 according to ‘Derived.SEER.Combined.T..2016.2017’, and as c0 according to ‘Derived.SEER.Combined.N..2016.2017’ and ‘Derived.SEER.Combined.M..2016.2017’; (V) the surgical procedure was breast-conserving surgery (BCS); (VI) the number of detected regional nodes was between 0 and 5, as recorded in ‘Regional.nodes.examined…1988...’. It should be noted that due to the lack of detailed information on axillary lymph node surgery in the SEER database, and after reviewing relevant literature, we defined patients with 0 detected lymph nodes as those who did not undergo any axillary surgery, and those with 1–5 detected lymph nodes as patients who underwent SLNB (20). (VII) The patient received postoperative radiotherapy. Exclusion criteria were as follows: (I) follow-up time of less than one month; (II) missing key information, such as race, marital status, or BC subtype (Figure 1).

Figure 1.

Flowchart of the study. BCS, breast-conserving surgery; SEER, Surveillance, Epidemiology, and End Results; SLNB, sentinel lymph node biopsy; PSM, propensity score matching.

Variable selection

The specific study variables included the following: age at diagnosis (<40, 40–49, 50–64, ≥65 years); year of diagnosis (2016, 2017); race (White, Black, other); marital status (married, unmarried); pathological type (infiltrating duct carcinoma, other); tumor location (left, right); American Joint Committee on Cancer (AJCC) 7th edition T staging (T1, T2); chemotherapy status (yes, no); and grade (I-II, III, unknown).

Statistical analyses

The main outcome measure of this study is OS, with breast cancer-specific survival (BCSS) serving as the secondary outcome. OS is defined as the period from the diagnosis of the disease (or the start of treatment) to death from any cause. BCSS refers to the length of time a patient survives after a BC diagnosis, without dying from causes unrelated to BC. Specifically, it is the time from the date of diagnosis to the date of death due to BC or its complications (21). The population was divided into two groups: the BCS group and the BCS plus SLNB group. Baseline characteristics between the two groups were compared using t-tests and Chi-squared tests. To address baseline differences, propensity score matching (PSM) with a caliper value of 0.1 was subsequently performed. Kaplan-Meier (KM) survival curves and log-rank tests were utilized to assess differences in OS and BCSS between the groups. Furthermore, both univariate and multivariate Cox regression analyses were carried out to identify independent risk factors for OS and BCSS. Subgroup analyses were performed to examine the potential influence of axillary surgery on survival outcomes in this cohort. Statistical significance was set at a two-sided p-value of less than 0.05, and data analysis was conducted using R software (version 4.4.1; http://www.R-project.org/).

Results

Baseline characteristics

Based on our inclusion and exclusion criteria, a total of 1,470, patients were included in this study, of whom 215 underwent only BCS, and 1,255 underwent BCS combined with SLNB (Figure 1).

In terms of tumor features, the BCS group exhibited less aggressiveness. Specifically, this was reflected by a lower grade (BCS, Grade I–II, 56.7% vs. BCS + SLNB, Grade I-II, 40.6%; P<0.001) and a lower T-stage (BCS, T1, 61.4% vs. BCS + SLNB, T1, 30.3%; P<0.001). Additionally, a higher proportion of triple-negative cases was observed in the BCS + SLNB group (BCS, HR⁻/HER2⁻, 19.1% vs. BCS + SLNB, HR⁻/HER2⁻, 28.5%; P<0.001). In terms of demographic characteristics, patients in the BCS group were older on average (BCS, ≥65 years, 38.6% vs. BCS + SLNB, ≥65 years, 26.5%; P=0.003). A larger proportion of patients in the BCS group were diagnosed in 2017 (BCS, diagnosed in 2017, 58.1% vs. BCS + SLNB, diagnosed in 2017, 52.0%; P=0.11). Notably, nearly half of the patients in the BCS group declined chemotherapy (BCS, no chemotherapy performed, 44.2% vs. BCS + SLNB, no chemotherapy performed, 15.9%; P<0.001) (Table 1). This observation may reflect either clinician-guided exemptions based on low-risk criteria or patient preferences, given that 61.4% of the BCS group had T1-stage disease and 56.7% were of the HR⁺/HER2⁻ subtype (22,23).

Table 1. Demographic, clinical, and laboratory features of cT1–2N0M0 breast cancer patients who underwent radiotherapy before PSM.

Variables	Initial cohort, n (%)		P
	BCS (N=215)	BCS + SLNB (N=1,255)
Age (years)			0.003
<40	12 (5.6)	97 (7.7)
40–49	34 (15.8)	248 (19.8)
50–64	86 (40.0)	577 (46.0)
≥65	83 (38.6)	333 (26.5)
Race			0.13
White	174 (80.9)	936 (74.6)
Black	20 (9.3)	161 (12.8)
Other	21 (9.8)	158 (12.6)
Marital status			0.51
Married	179 (83.3)	1,070 (85.3)
Unmarried	36 (16.7)	185 (14.7)
Laterality			>0.99
Left	106 (49.3)	619 (49.3)
Right	109 (50.7)	636 (50.7)
Histopathology			0.19
Duct carcinoma	177 (82.3)	1,079 (86.0)
Other	38 (17.7)	176 (14.0)
Grade			<0.001
I–II	122 (56.7)	510 (40.6)
III	73 (34.0)	678 (54.0)
Unknown	20 (9.3)	67 (5.3)
Subtype			<0.001
HR−/HER2−	41 (19.1)	358 (28.5)
HR−/HER2+	12 (5.6)	134 (10.7)
HR+/HER2−	122 (56.7)	379 (30.2)
HR+/HER2+	40 (18.6)	384 (30.6)
T			<0.001
T1	132 (61.4)	380 (30.3)
T2	83 (38.6)	875 (69.7)
Year of diagnosis			0.11
2016	90 (41.9)	602 (48.0)
2017	125 (58.1)	653 (52.0)
Chemotherapy			<0.001
No/unknown	95 (44.2)	200 (15.9)
Yes	120 (55.8)	1,055 (84.1)

For race, other includes American Indian, Alaska Native, Asian, and Pacific Islander. BCS, breast-conserving surgery; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; PSM, propensity score matching; SLNB, sentinel lymph node biopsy; T, tumor.

Cox proportional hazards regression analysis

We performed univariate and multivariate Cox regression analyses on the OS and BCSS of the patients to identify its independent risk factors. As shown in Table 2, for OS, the univariate Cox analysis indicated that age, subtype and surgery type were associated with the OS of patients. After performing multivariate Cox regression analysis, we observed that patients aged 65 years or older tend to have relatively poorer OS (hazard ratio, 1.36–7.73; P=0.02), whereas those with BC subtypes that are HR-positive and HER2-positive demonstrate relatively better OS (hazard ratio, 0.23–0.67; P=0.004). Furthermore, the performance of SLNB does not seem to influence OS, which is consistent with findings from previous studies (14,15,24,25).

Table 2. Univariate and multivariate Cox regression analyses of OS in the general population.

Variables	Univariate analysis			Multivariate analysis
	Hazard ratio (95% CI)	P		Hazard ratio (95% CI)	P
Age (years)
<40	Reference			Reference
40–49	1.23 (0.39–3.81)	0.71		1.27 (0.49–3.29)	0.67
50–64	1.25 (0.43–3.55)	0.67		1.31 (0.54–3.16)	0.60
≥65	3.17 (1.14–8.83)	0.02		3.25 (1.36–7.73)	0.02
Race
White	Reference			Reference
Black	0.65 (0.31–1.35)	0.25		–
Other	0.93 (0.49–1.75)	0.82		–
Marital status
Married	Reference			Reference
Unmarried	0.77 (0.41–1.45)	0.43		–
Laterality
Left	Reference			Reference
Right	0.77 (0.51–1.17)	0.23		–
Histopathology
Duct carcinoma	Reference			Reference
Other	0.81 (0.43–1.53)	0.53		–
Grade
I–II	Reference			Reference
III	1.20 (0.78–1.85)	0.40		–
Unknown	1.29 (0.54–3.08)	0.55		–
Subtype
HR−/HER2−	Reference			Reference
HR−/HER2+	0.84 (0.41–1.17)	0.63		0.84 (0.46–1.53)	0.63
HR+/HER2−	0.87 (0.53–1.41)	0.58		0.65 (0.42–1.00)	0.10
HR+/HER2+	0.39 (0.21–0.75)	0.004		0.40 (0.23–0.67)	0.004
T
T1	Reference			Reference
T2	1.11 (0.71–1.72)	0.64		–
Year of diagnosis
2016	Reference			Reference
2017	0.86 (0.55–1.34)	0.51		–
Chemotherapy
No/unknown	Reference			Reference
Yes	0.68 (0.42–1.09)	0.11		–
Surgery
BCS	Reference			Reference
BCS + SLNB	0.57 (0.35–0.94)	0.03		0.65 (0.42–1.01)	0.11

For race, other includes American Indian, Alaska Native, Asian, and Pacific Islander. BCS, breast-conserving surgery; CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; OS, overall survival; SLNB, sentinel lymph node biopsy; T, tumor.

Similarly, after performing both univariate and multivariate Cox regression analyses on patients’ BCSS, it was found that only molecular subtype had an impact on BCSS, while the performance of SLNB did not affect patients’ survival (Table 3).

Table 3. Univariate and multivariate Cox regression analyses of BCSS in the general population.

Variables	Univariate analysis			Multivariate analysis
	Hazard ratio (95% CI)	P		Hazard ratio (95% CI)	P
Age (years)
<40	Reference			Reference
40–49	0.83 (0.25–2.75)	0.76
50–64	0.87 (0.29–2.55)	0.80
≥65	1.04 (0.34–3.16)	0.94
Race
White	Reference			Reference
Black	0.84 (0.38–1.85)	0.72
Other	1.23 (0.62–2.44)	0.61
Marital status
Married	Reference			Reference
Unmarried	0.67 (0.31–1.47)	0.41
Laterality
Left	Reference			Reference
Right	0.62 (0.34–1.12)	0.11
Histopathology
Duct carcinoma	Reference			Reference
Other	0.56 (0.20–1.56)	0.26
Grade
I–II	Reference			Reference
III	2.04 (1.16–3.59)	0.04		1.57 (0.83–2.98)	0.23
Unknown	3.06 (1.27–7.36)	0.03		2.41 (0.98–5.94)	0.10
Subtype
HR−/HER2−	Reference			Reference
HR−/HER2+	0.90 (0.38–2.15)	0.82		0.89 (0.43–1.84)	0.80
HR+/HER2−	0.63 (0.32–1.21)	0.16		0.86 (0.47–1.60)	0.70
HR+/HER2+	0.13 (0.03–0.44)	0.001		0.15 (0.05–0.43)	0.002
T
T1	Reference			Reference
T2	2.15 (1.16–3.96)	0.03		2.02 (1.08–3.77)	0.06
Year of diagnosis
2016	Reference			Reference
2017	0.99 (0.54–1.82)	0.99
Chemotherapy
No/unknown	Reference			Reference
Yes	1.95 (0.89–4.27)	0.15
Surgery
BCS	Reference			Reference
BCS + SLNB	0.89 (0.39–1.99)	0.75

For race, other includes American Indian, Alaska Native, Asian, and Pacific Islander. BCS, breast-conserving surgery; BCSS, breast cancer-specific survival; CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; SLNB, sentinel lymph node biopsy; T, tumor.

Survival analysis of patients before and after PSM

To investigate whether SLNB impacts survival in the target population, we performed KM analysis of OS and BCSS for the populations before and after PSM. It was observed that, before PSM, SLNB improved OS in patients who underwent BCS for early-stage BC (P=0.03), while there was no significant improvement in BCSS (P=0.78). To ensure comparability between the groups and eliminate confounding bias, we performed 1:1 PSM with a caliper value of 0.1. PSM could reduce selection bias by matching individuals with similar characteristics, improving the validity of comparisons (26). A total of 208 patient pairs were successfully matched, with no significant differences observed between the groups across the various variables (Table 4). And no significant difference in OS or BCSS was found between patients who underwent SLNB and those who did not (OS, P=0.07; BCSS, P=0.30) (Figure 2).

Table 4. Demographic, clinical, and laboratory features of cT1–2N0M0 breast cancer patients who underwent radiotherapy after PSM.

Variables	PSM cohort, n (%)		P
	BCS (N=208)	BCS + SLNB (N=208)
Age (years)			0.92
<40	12 (5.8)	9 (4.3)
40–49	34 (16.3)	33 (15.9)
50–64	85 (40.9)	87 (41.8)
≥65	77 (37.0)	79 (38.0)
Race			0.48
White	167 (80.3)	157 (75.5)
Black	20 (9.6)	26 (12.5)
Other	21 (10.1)	25 (12.0)
Marital status			0.34
Married	172 (82.7)	180 (86.5)
Unmarried	36 (17.3)	28 (13.5)
Laterality			0.69
Left	100 (48.1)	105 (50.5)
Right	108 (51.9)	103 (49.5)
Histopathology			0.80
Duct carcinoma	171 (82.2)	168 (80.8)
Other	37 (17.8)	40 (19.2)
Grade			0.97
I–II	122 (58.7)	124 (59.6)
III	72 (34.6)	71 (34.1)
Unknown	14 (6.7)	13 (6.3)
Subtype			0.99
HR−/HER2−	40 (19.2)	39 (18.8)
HR−/HER2+	12 (5.8)	11 (5.3)
HR+/HER2−	116 (55.8)	117 (56.3)
HR+/HER2+	40 (19.2)	41 (19.7)
T
T1	125 (60.1)	126 (60.6)
T2	83 (39.9)	82 (39.4)
Year of diagnosis			0.16
2016	87 (41.8)	102 (49.0)
2017	121 (58.2)	106 (51.0)
Chemotherapy			>0.99
No/unknown	89 (42.8)	88 (42.3)
Yes	119 (57.2)	120 (57.7)

For race, other includes American Indian, Alaska Native, Asian, and Pacific Islander. BCS, breast-conserving surgery; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; M, metastasis; N, node; PSM, propensity score matching; SLNB, sentinel lymph node biopsy; T, tumor.

Figure 2.

The Kaplan-Meier survival curves of the effect of SLNB on OS (A) and BCSS (C) in the overall population before PSM, and its effect on OS (B) and BCSS (D) in the overall population after PSM. BCS, breast-conserving surgery; BCSS, breast cancer-specific survival; PSM, propensity score matching; SLNB, sentinel lymph node biopsy.

In both the INSEMA and SOUND studies, patients with stage T2 accounted for only about 10% of the total study population. Therefore, a subgroup analysis based on T staging was performed after PSM. As shown in Figure 3, neither T1 nor T2 tumors were influenced by SLNB regarding OS (T1, P=0.06; T2, P=0.50) and BCSS (T1, P=0.15; T2, P=0.63). This further supports the clinical feasibility of omitting SLNB for this subset of clinically node-negative (cN0) patients.

Figure 3.

The Kaplan-Meier survival curves of the effect of SLNB on OS in the T1 cohort (A), the T2 cohort (C), as well as the effect of SLNB on BCSS in the T1 cohort (B), the T2 (D) cohort after PSM. BCS, breast-conserving surgery; BCSS, breast cancer-specific survival; OS, overall survival; PSM, propensity score matching; SLNB, sentinel lymph node biopsy; T, tumor.

Discussion

According to 2024 BC statistics, while global incidence rates continue to rise, overall mortality has declined by 44% from 1989 to 2022. Precision and individualized treatment are now standard for early-stage BC patients with a favorable prognosis. This includes optimized axillary surgery management as part of comprehensive care (27). In fact, BC axillary surgery has evolved toward less invasive approaches, particularly with SLNB. The ACOSOG Z0011 trial followed 891 patients with T1 tumors and 1–2 positive sentinel nodes for up to 10 years. It ultimately showed no significant OS difference between SLNB and ALND groups (9). Subsequently, many other studies have further validated this finding (28-31). This shift in clinical practice has led to further exploration of the possibility that, in certain patient populations, even SLNB may be omitted without compromising survival outcomes.

A 2022 meta-analysis by Davey et al. reported that patients with ductal carcinoma in situ (DCIS) had an absolute risk of <5% and a relative risk of <1% for SLNB positivity (32). Such a low detection rate challenges the clinical utility of routine SLNB in DCIS management. The SOUND trial studied early-stage BC patients (tumors ≤2 cm, cN0 by ultrasound). It demonstrated that omitting axillary surgery was non-inferior to SLNB for 5-year disease-free survival (DFS) (14). The study also revealed that, in the group of patients who did not undergo axillary surgery, the cumulative incidence of lymph node recurrences in the axilla was very low—only 0.4% at 5 years. The SLNB group showed 13.7% nodal involvement with low recurrence rates. This suggests axillary surgery may be unnecessary for early-stage cN0 BC patients (14). Furthermore, the primary results of the recent INSEMA trial have been published. This trial enrolled clinically node-negative T1/T2 invasive BC patients (90% cT1, 79% pT1). After 6-year median follow-up, omitting axillary staging proved noninferior to SLNB (15). These suggest that, for many patients, the removal of axillary lymph nodes serves more as a staging procedure rather than a therapeutic intervention.

However, although the findings from the previous studies are promising, it remains important to consider the generalizability of these results (13,33,34). The SOUND and INSEMA trials included patients with small (T1) tumors, and the evidence for omitting axillary surgery in patients with larger (T2) tumors is still inconclusive and requires further investigation. Further research is needed to assess whether these findings can be applied to higher-risk patients.

Thus, in this study, we performed additional validation analyses using SEER datasets. After analyzing the baseline characteristics of the BCS and BCS + SLNB groups, we found that the BCS group had a lower tumor T-stage and grade. It also had a higher proportion of HR⁺/HER2⁻ patients and older age. These factors may explain why these patients were exempt from SLNB. Before PSM, we found that performing SLNB could prolong patients’ OS (P=0.03), but had no effect on BCSS (P=0.78). After adjusting for baseline characteristics, we found that SLNB did not improve patients’ survival outcomes, either in terms of OS (P=0.07) or BCSS (P=0.30), consistent with prior studies. To further identify high-risk factors affecting prognosis in this population, we performed Cox regression analyses of OS and BCSS. Multivariate analysis identified age and molecular subtype as significant prognostic factors for OS, while age failed to demonstrate independent prognostic value for BCSS. This likely reflects the impact of competing non-cancer mortality on OS but not BCSS in older patients (35,36). Therefore, given the unique characteristics of older adults, conservative treatment approaches are often clinically preferred. Recent studies increasingly recommend omitting radiotherapy in early-stage elderly patients (37,38). This also indirectly supports the feasibility of omitting SLNB in this population, since its primary role is diagnostic rather than therapeutic. In the present study, molecular subtype was identified as a significant prognostic factor for both OS and BCSS, consistent with previous research findings (39,40). In general, HR⁺ BC tend to do better. The HR⁺/HER2⁻ type has the highest survival rates and triple-negative BC is the most aggressive subtype (41). Of note, T-stage showed borderline significance for BCSS (P=0.06). As an established prognostic factor, higher T-stage generally correlates with increased risks of vascular and tissue invasion. Given that most patients in previous studies were staged as T1, this could introduce bias in the results. Therefore, we performed a subgroup analysis based on T stage. The results showed that, regardless of T stage (T1/T2), axillary surgery did not improve prognosis. This suggests that in clinical practice, SLNB can be omitted for patients with cT1–2N0M0 stage.

To the best of our knowledge, although several similar studies have been published with consistent conclusions, our study represents the first SEER database analysis employing strictly defined clinical TNM staging criteria (42-45). In this study, we carefully selected the target population based on the “cN0” standard from the SEER database and further refined the study cohort using PSM, minimizing selection bias in the analysis. Additionally, we addressed the issue of an excessive number of T1 patients in previous studies and further validated that omitting SLNB is feasible for this group of cT1–2N0M0 patients. There are several limitations in this study. First, to maintain study rigor, we only included patients with complete cTNM staging data from the 2016–2017 SEER database. This selection criterion may have resulted in limited sample size, potentially impacting the findings. Second, the SEER database lacks detailed axillary surgery records. We therefore used detected lymph node count as an SLNB proxy, though this may not perfectly match clinical practice. Lastly, despite using PSM, potential confounding factors may still influence the results due to the inherent limitations of the SEER database. In conclusion, this study aims to further validate the SOUND and INSEMA studies, address any potential limitations, and improve current treatment protocols to spare this group of early BC patients from axillary surgery.

Conclusions

This study is based on the large SEER database and focuses on patients with cT1–2N0M0 BC. We found that regardless of whether the patients were classified as T1 or T2, the decision to perform SLNB did not impact their prognosis. This conclusion aligns with findings from previous studies, suggesting that these patients may avoid the trauma of axillary surgery in clinical practice.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.