Current surgical standards in the management of the axilla

The origins of the sentinel node concept did not lie in breast surgery but rather in melanoma management. Dermatologic surgeons first employed radiocolloids and dyes to identify the primary draining node of a tumor field [3]. Armando Giuliano later adapted this approach for early stage breast cancer, demonstrating that detection of the sentinel node was feasible and represented an accurate staging method of the axilla [4]. Only a few years later, randomized studies confirmed that sentinel lymph node biopsy (SLNB) provided equivalent oncologic safety to axillary lymph node dissection (ALND) in clinically node-negative disease when breast-conserving surgery was planned [5‐7]. The term “sentinel lymph node biopsy,” widely adopted in English-language literature, should not be confused with diagnostic core needle biopsy or fine-needle aspiration; rather, it refers to the surgical excision of the sentinel node performed at the time of breast surgery.

Subsequent trials further refined the role of SLNB, showing that axillary dissection could often be omitted even in cases with limited sentinel node metastases, particularly when adjuvant radiotherapy was administered to the lymphatic drainage areas [8, 9]. Most recently, data from two large prospective randomized studies—INSEMA and SOUND—suggest that in carefully selected patients with low-risk disease and clinically negative axilla, the sentinel lymph node biopsy itself may be safely avoided as a staging procedure.

The INSEMA trial [10] enrolled 5502 women aged 18 years or older with T1- or T2-stage invasive breast cancer and no clinical or sonographic evidence of nodal involvement. All patients underwent breast-conserving surgery and were randomized in a 1:4 ratio to either SLNB or omission of SLNB. The per-protocol population included 4858 patients, of whom 962 had no axillary surgery. The study population reflected a typical low-risk cohort: 89% were aged 50 years or older, 95% had hormone receptor-positive/HER2-negative tumors, 96% were G1–G2, and 87% had a Ki-67 ≤ 20%. In the SLNB arm, 3.5% of patients had micrometastases and 11.6% macrometastatic involvement, mostly classified as pN1. All participants received whole-breast irradiation according to protocol; nodal irradiation was not planned, although dosimetric analyses later revealed that up to half of patients received substantial incidental radiation doses to axillary level I.

After a median follow-up of 74 months, the 5‑year invasive disease-free survival was nearly identical between groups (91.9% without SLNB vs. 91.7% with SLNB; hazard ratio 0.91; 95% confidence interval [CI] 0.73–1.14), meeting the prespecified noninferiority margin. These findings provide robust evidence that omission of SLNB does not compromise oncologic outcomes in this population.

The SOUND study [11] addressed a similar question in 1463 patients with tumors ≤ 2 cm (cT1) and negative axillary ultrasound findings, all of whom underwent breast-conserving surgery followed by radiotherapy. Patients were randomized 1:1 to SLNB or no axillary surgery. The cohort again reflected a predominantly postmenopausal, low-risk group: 81% were older than 50 years, 88% had hormone receptor-positive/HER2-negative disease, 82% of the tumors were G1–G2, and 64% had Ki-67 ≤ 20%. In the SLNB arm, 14% of patients were node-positive (5% micrometastases, 8% pN1, 1% pN2). After a median follow-up of 68 months, there were no significant differences in local–regional recurrence (1.7% vs. 1.6%) or in 5‑year distant metastasis-free survival (97.7% vs. 98.0%; p = 0.67). Thus, the SOUND trial confirmed that omission of SLNB in selected low-risk patients is oncologically safe.

Based on these data, the ASCO Clinical Practice Guidelines on SLNB in early breast cancer were updated in 2025 [12]. They now recommend that in postmenopausal women aged ≥ 50 years with unifocal, hormone receptor-positive/HER2-negative ductal carcinoma measuring < 2 cm (cT1), clinically and sonographically negative axilla, grade G1–G2, and Ki-67 < 20%, SLNB may be safely omitted (Fig. 1). Since both INSEMA and SOUND included only female participants, this recommendation currently applies to women only and not to male breast cancer patients.

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At the San Antonio Breast Cancer Symposium in December 2025, results from the Dutch BOOG 13-08 trial [13], which applied similar inclusion criteria, were presented. The investigators concluded that SLNB can be safely omitted in a low-risk patient cohort. The primary endpoint of the study, 5‑year regional recurrence-free survival (RRFS), did not differ between patients who underwent SLNB and those who did not.

In detail, patients who underwent SLNB achieved a 5-year RRFS of 96.6% (95% CI 95.2–98.0%), compared with 94.2% (95% CI 92.4–96.0%) in patients without SLNB. This corresponds to an absolute difference of 2.35%, which did not exceed the predefined noninferiority margin of 5%. In the SLNB cohort, 13.7% of patients had a positive sentinel lymph node, including 6.0% with micrometastases and 7.7% with macrometastases. These rates are comparable to those reported in the SOUND and INSEMA trials.

However, a notably higher rate of distant metastatic disease was observed in the non-SLNB group of the BOOG 13-08 trial (3.6%) compared with the corresponding groups in the SOUND (2.0%) and INSEMA (2.7%) studies. When applying the ASCO guideline criteria (age ≥ 50 years, cT1–2, hormone receptor +/HER2− breast cancer, and histologic grade 1–2), a subgroup of 949 patients was identified in whom the distant metastasis rate was 2.2%, comparable to that observed in the other two trials. An additional noteworthy finding was that only approximately 44% of patients in the BOOG 13-08 trial received endocrine therapy, despite 87% having hormone receptor-positive breast cancer. This may have influenced oncologic outcomes and should be considered when interpreting the results.

Results from the ongoing NAUTILUS trial (NCT04303715) are still awaited and may further consolidate this evidence.

An important consideration is the potential loss of prognostic and therapeutic information when SLNB is omitted. In both major trials, a substantial proportion of patients received adjuvant chemotherapy—12% in the SLNB arm and 10% in the non-SLNB arm of INSEMA, and 20.1% and 17.5%, respectively, in SOUND—indicating that systemic therapy decisions were primarily driven by tumor biology rather than nodal status. Nevertheless, nodal information remains relevant for certain prognostic tools, including the EPClin risk score [14] and the freely accessible CTS5 calculator [15], which estimate late recurrence risk after endocrine therapy and rely partly on nodal data.

The omission of SLNB may also affect the identification of patients eligible for CDK4/6 inhibitor therapy. In INSEMA, only 0.2% of patients had four or more positive nodes, the current criterion for adjuvant abemaciclib [16], suggesting minimal overlap with this low-risk population. However, for ribociclib [17], node positivity plays a greater role in defining eligibility. A recent analysis by Wanis et al. of 119,312 patients with cT1cN0 hormone receptor-positive breast cancer found that 7.5% met criteria for ribociclib treatment solely based on sentinel node findings [18]. This subgroup would potentially remain unidentified if SLNB was omitted. Therefore, in patients with adverse histopathological features in the resection specimen—such as higher grade, elevated Ki-67, or lymphovascular invasion—a secondary or delayed SLNB may be considered to guide systemic therapy decisions.

Another key point concerns radiotherapy. In all three trials, whole-breast irradiation was consistently applied (INSEMA and BOOG 13-08: 100%, SOUND: > 80%), which limits the transferability of these results to alternative radiation protocols such as partial-breast irradiation, the hypofractionated Fast-Forward regimen [19], or even omission of radiotherapy in selected low-risk populations. Consequently, a simultaneous de-escalation of both surgery and radiotherapy cannot currently be recommended. The oncologic safety observed in these trials relies on the consistent use of whole-breast irradiation, and its applicability to alternative radiotherapy regimens remains uncertain. Any such modification of treatment should therefore be carefully individualized and discussed with the patient, taking individual risk factors into account.

In conclusion, axillary surgery has evolved from radical dissection to an increasingly individualized approach. SLNB remains the current standard for most patients. However, in patients with low-risk disease undergoing breast-conserving therapy with mandatory whole-breast irradiation, mounting evidence suggests that this procedure may be safely omitted in a carefully defined subgroup. While this de-escalation represents a major step toward minimizing treatment morbidity, the sentinel node still provides prognostic and therapeutic information relevant to systemic management. Ongoing research will clarify how imaging, molecular diagnostics, and radiotherapy strategies can complement surgical minimalism while preserving oncologic safety—the ultimate priority in modern breast cancer care.