The SOUND (NCT02167490) and INSEMA (NCT02466737) trials examined whether sentinel lymph node biopsy (SLNB) can be safely omitted in selected patients with early-stage breast cancer. Both randomized studies enrolled patients with sonographically normal axillary nodes who were assigned to SLNB or no axillary surgery; nearly all patients received adjuvant whole-breast radiation, and most were older than 50 with hormone receptor–positive tumors under 2 cm.
At 5 to 6 years of follow-up neither trial showed a statistically significant difference in key outcomes. In SOUND, 5-year distant disease–free survival was 97.7% with SLNB versus 98.0% without axillary surgery (hazard ratio 0.84; 90% CI, 0.45–1.54). In INSEMA, estimated 5-year invasive disease–free survival was 91.9% in the surgery-omission arm versus 91.7% in the surgery arm (HR 0.91; 95% CI, 0.73–1.14). Both trials reported exceptionally low axillary recurrence rates — about 1% or less at 5–6 years.
Sunil Dutta, MD, assistant professor of radiation oncology at Emory University School of Medicine, said the findings reinforce a trend toward de-escalating axillary surgery in carefully selected patients. He noted the central questions now are whether modest incidental dose to level 1 axilla from tangential breast fields or the effects of systemic therapy — particularly endocrine therapy — account for the low nodal recurrence rates, and how long any apparent control will persist beyond 5–6 years.
Quality-assurance review in INSEMA suggested standard whole-breast fields delivered roughly 80% of the prescription dose to level 1 axilla in about half of plans evaluated, but coverage varied with patient anatomy and field design. Dutta cautioned that neither high tangents nor incidental nodal coverage have been tested prospectively as a substitute for planned nodal treatment, and the trials did not mandate intentional nodal irradiation.
Patients who meet criteria for omission of SLNB rarely have other indications for regional nodal irradiation (RNI); those requiring RNI typically present with clinically involved nodes or larger tumors and would have been ineligible for SOUND or INSEMA. When nodal treatment is indicated, Dutta recommends using a dedicated supraclavicular field rather than relying on high tangents, which he does not consider standard of care given the lack of prospective evidence.
On balancing nodal coverage with sparing of heart and lung, Dutta said high tangents cause only a small increase in upper-lung dose when treating the breast alone, and heart-sparing techniques such as breath-hold or prone positioning can mitigate cardiac exposure, particularly for left-sided tumors. Intentional internal mammary or supraclavicular fields significantly raise lung and cardiac doses and should be used only when clinically indicated.
For isolated, pathologically confirmed axillary recurrence after omission of SLNB, the recommended salvage approach is thorough restaging followed by multidisciplinary discussion. Management commonly includes consideration of systemic therapy first, surgery if resectable, and radiation to the supraclavicular/axillary region while avoiding unnecessary re-irradiation of the breast. Careful field matching is essential to limit cumulative dose to critical structures such as the brachial plexus and reduce the risk of brachial plexopathy.
Dutta also noted that one historical rationale for high tangents was facilitating moderately hypofractionated treatment courses by avoiding nodal fields; however, emerging data and updated ASTRO guidance support hypofractionation for breast and nodal treatments alike, reducing that particular advantage of high tangents.
Prospective questions remain about management of limited nodal disease. The phase 3 MA.39 (TAILOR RT) trial is testing RNI versus whole-breast irradiation alone in patients with limited node-positive disease and low Oncotype scores; its results may further clarify indications for nodal treatment. Until then, treatment decisions should be individualized and made by a multidisciplinary team, weighing trial eligibility, tumor biology, anatomic considerations, and long-term risks.
References: Gentilini OD et al., JAMA Oncol. 2023;9(11):1557-1564. Reimer T et al., N Engl J Med. 2025;392(11):1051-1064.
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