The international non-inferiority SENOMAC trial has confirmed that omitting completion axillary lymph node dissection (ALND) is oncologically safe (ie, a less intensive approach does not compromise outcomes) and substantially reduces patient-reported arm morbidity in patients with one or two sentinel lymph node macrometastases—including patients with T2–T3 tumors and those undergoing mastectomy, Swedish investigators reported at the 2026 ASCO Annual Meeting.¹

“Our findings suggest that omission of completion axillary lymph node dissection should be the standard of care in breast cancer that has spread to only one to two sentinel lymph nodes,” said Jana de Boniface, MD, PhD, of Capio St. Göran’s Hospital and the Karolinska Institutet in Stockholm.

Our findings suggest that omission of completion axillary lymph node dissection should be the standard of care in breast cancer that has spread to one to two sentinel lymph nodes.

— JANA DE BONIFACE, MD, PhD

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What makes this trial different from previous studies is that 36% of patients in the study population were undergoing mastectomy. Dr. de Boniface further emphasized that the recommendations stemming from SENOMAC’s findings should be viewed in context of the trial design: most patients in the study received adjuvant locoregional radiotherapy.

Need for the Study

ALND has long been standard practice following a positive sentinel lymph node biopsy in breast cancer; however, ALND carries significant risks of arm-related morbidity, including lymphedema, reduced range of motion, and chronic pain. Earlier trials, notably ACOSOG Z0011,2 suggested that ALND could be safely omitted in select patients but were limited by their focus on breast-conserving surgery and smaller tumors (< 5 cm), Dr. de Boniface pointed out.

Designed to address these gaps, SENOMAC is the largest randomized trial to evaluate ALND omission in patients with one or two sentinel lymph node macrometastases. Most importantly, it enrolled patients with larger tumors (T3, 5.8% of patients) and those undergoing mastectomy (36%)—populations previously excluded from trials in this space.

SENOMAC Design

SENOMAC enrolled 2,766 patients, median age 61, from five countries (primarily Sweden and Denmark) with primary invasive, clinically node-negative T1–T3 breast cancer and up to two sentinel node macrometastases (> 2 mm); 87% had estrogen receptor-positive, HER2-negative tumors. Patients were randomized 1:1 to completion ALND or omission of ALND. Adjuvant radiotherapy and systemic therapy followed local standards of care.

The primary endpoint was overall survival, with non-inferiority to be declared if the upper boundary of the one-sided 90% confidence interval (CI) for the hazard ratio (HR) fell below 1.44, using the ALND group as reference; breast cancer-specific survival was a secondary endpoint. Patient-reported outcomes, including arm morbidity (Lymph-ICF questionnaire) and health-related quality of life (EORTC QLQ-C30 and BR23), were assessed at 1, 3, and 5 years; these questionnaires were completed by more than 80% of participants.

The per-protocol population comprised 2,540 patients, of whom 919 (36%) were undergoing mastectomy. Almost all patients underwent radiotherapy and adjuvant endocrine therapy; about two-thirds also received chemotherapy, with no difference between the arms (chemotherapy use rates varied between countries; however, chemotherapy use between the two arms was balanced). Median follow-up was 60.1 months.

Key Results

“Overall survival was equivalent in both groups. The survival curves exactly overlapped,” Dr. de Boniface said. At a median follow-up of about 5 years, 196 patients had died, 74 of the deaths attributable to breast cancer.

The overall survival rate at 5 years was 93.4% in the ALND group and 94.4% in the omission group (HR 0.89; 95% CI, 0.67-1.17; P = .001 for non-inferiority). “Importantly, the upper limit of the confidence interval was required to be below 1.44 to confirm non-inferiority, and you see the hazard ratio is actually far below that requirement,” she noted. 

Breast-cancer specific survival at 5 years was 97.9% in the omission group and 97.2% in the ALND group (HR, 0.75; 95% CI, 0.45-1.27).

In the group having completion ALND, additional cancer was found in the lymph nodes in 34.5%. Final nodal stage was pN1 for the vast majority of patients in both groups but was reported as pN2-3 for 12.5% of the completion ALND group compared to 0.5% of the omission group.

One sentinel node macrometastasis was identified in 84.6%. Additional sentinel node micrometastases were found in 10.2% of these patients. For the ALND and omission groups, respectively, regional recurrences were observed in 0.6% and 0.7% and distant recurrences in 5.5% and 4.9%. The findings were consistent across subgroups, she further reported.

Arm Morbidity and Quality of Life

For global health and quality of life, all time points showed either statistically significant improvements or favorable trends favoring omission of ALND. For arm symptoms, differences favoring the omission of ALND were seen at every time point and were both statistically significant and clinically relevant. Dr. de Boniface specifically noted that the difference in arm symptoms observed at study initiation persisted over time. Physical function of the arm showed a similar persistent separation between treatment groups; when evaluated categorically, these effects were rated as severe or very severe by 12.6% of patients undergoing completion ALND vs 3.6% of those omitting ALND (P < .001).

Dr. de Boniface was asked, in a press briefing, whether the findings might warrant a change in treatment guidelines. She responded that the omission of completion ALND is not typically recommended for patients who have undergone mastectomy, so in this group, the findings may have a real impact. “I think this is the only trial with a decent number of such patients—over 900, which is far beyond that of any other trial. So yes, I think for that group, they will,” she said. “For patients with breast-conserving surgery, I think most countries turned away from completion ALND after ACOSOG Z0011.2 For this group, we are delivering further data and with larger subgroups.” ν

DISCLOSURE: Dr. de Boniface had no relevant disclosures.

REFERENCES

1. de Boniface J, Tvedskov TF, Ryden L, et al: Omission of completion axillary dissection in patients with breast cancer and sentinel lymph node macrometastases: Overall survival and patient-reported arm morbidity from the randomized SENOMAC trial. 2026 ASCO Annual Meeting. Abstract LBA503. Presented May 30, 2026.

2. Giuliano AE, Ballman KV, Linda McCall L, et al: Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA 318:918-926, 2017.

EXPERT POINT OF VIEW

Judy C. Boughey, MD, the W.H. Odell Professor of Individualized Medicine and Professor of Surgery, Mayo Clinic, Rochester,was the invited discussant for the international non-inferiority SENOMAC trial reported by Swedish investigators at the 2026 ASCO Annual Meeting.¹ Dr. Boughey said completion axillary lymph node dissection (ALND) should be the standard of care in patients with breast cancer with one to two sentinel lymph nodes positive for macrometastases (ie, relatively large deposit of cancer (greater than 2 mm) found in one of those lymph nodes).

Judy C. Boughey, MD

“SENOMAC is obviously a very easy study for us to implement, it is widely generalizable, and it is cost-effective,” Dr. Boughey pointed out. “Patients are keen to avoid ALND, and this study allows us to expand the cohort of patients eligible for omission.”

She noted that the concept of omitting ALND in patients with pathologically node-positive disease first arose more than 2 decades ago with the ACOSOG Z0011 study.² For the next 20 years, other studies supported the de-escalation of axillary surgery, which has been reflected in data from the National Cancer Database: between 2018 and 2023, the rate of completion ALND in patients with clinically node-negative T1-T2 breast cancer with one or two positive sentinel nodes dropped from 34% to 14%, independent of breast cancer subtype, grade, and histology, she said.

“The areas where we have lagged behind in de-implementing ALND include patients undergoing mastectomy, patients found to have two positive nodes, those with larger tumors at presentation, ie, T3 disease,” she said. “This is the backdrop for the importance of the SENOMAC study.”

Omission of ALND Is Safe in Some Patients

Non-inferiority for the omission of ALND was clearly shown. Most importantly, she added, the findings provide reassurance that omission is safe in subgroups of patients that clinicians grapple with daily: those with invasive lobular disease (20% of the study population), those treated with mastectomy (36%), those with extranodal extension (34%). It also provides additional data, although smaller cohorts, supporting omission of ALND in patients with T3 disease (6%), those with two sentinel nodes positive for macrometastases (15%), and patients with triple-negative or HER2-positive breast cancer (13%).

Dr. Boughey did have a few additional discussion points. First, although patient-reported outcomes were clearly better among patients who avoided ALND, more contemporary surgical approaches, such as lymphovenous bypass, may reduce the morbidity associated with ALND. Second, she noted that while patients with clinically node-negative disease, including those with a negative axillary ultrasound, often undergo sentinel lymph node surgery to determine the extent of any nodal involvement, another “complexity that superimposes on the findings,” she said, comes from the recent SOUND³ and INSEMA⁴ trials in which carefully selected patients actually forego surgical axillary staging (ie sentinel lymph node surgery) altogether. These studies (omission of sentinel lymph node surgery and also omission of ALND in patients with positive sentinel nodes) then beg the question of whether de-escalation of surgery always warrants escalation of radiation. “To me, that’s a critical question,” she said.

‘Excellent, Well-Run Trial’

At a press briefing, ASCO Expert Jane L. Meisel, MD, FASCO, a Professor in the Department of Hematology and Medical Oncology as well as Gynecology and Obstetrics, and Codirector of Breast Medical Oncology, Emory University School of Medicine, congratulated the SENOMAC investigators on “this excellent and well-run clinical trial.”

Jane L. Meisel, MD, FASCO

“It’s so important to be looking at these questions and asking how we can possibly do less and achieve potentially the same or better outcomes,” Dr. Meisel said. “There are so many survivorship issues, such as lymphedema and arm function, that we don’t consider as much as we should in the context of thinking about curing breast cancer but these are things that continue to plague patients over the years. This study shows us that for patients whose breast cancer has spread to one to two sentinel lymph nodes, we can safely omit ALND, especially if patients are able to receive adjuvant local-regional radiation.”

Dr. Meisel noted a few things about SENOMAC to take into account: the study was randomized, which is a favorable factor; it included some patients with tumors larger than 5 cm, reflecting a real-life population; and it primarily enrolled patients from Sweden and Denmark, therefore lacking ethnic diversity, although she felt the results would nevertheless translate to other racial and ethnic populations.

“I do think, overall, the study adds strength to the idea that we probably could and should be doing less surgery on these patients with a lower burden of lymph node involvement,” Dr. Meisel concluded. “Putting the findings into clinical practice may allow us to improve arm physical function, appearance, body image, and so many other things for our breast cancer survivors all around the world. I’m excited to see what other clinicians make of these findings.” 

DISCLOSURE: Dr. Boughey had personal disclosures for UpToDate and CairnSurgical. Dr. Meisel has served as a consultant or advisor for AstraZeneca, GE HealthCare, Genentech, Novartis, Olema Oncology, Pfizer, SeaGen, Sermonix Pharmaceuticals, and Stemline.

REFERENCES

1. de Boniface J, Tvedskov TF, Ryden L, et al: Omission of completion axillary dissection in patients with breast cancer and sentinel lymph node macrometastases: SENOMAC trial. 2026 ASCO Annual Meeting. Abstract LBA503. Presented May 30, 2026.

2. Giuliano AE, Ballman KV, Linda McCall L, et al: Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA 318:918-926, 2017.

3. Gentilini OD, Botteri E, Sangalli C, et al: Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes. The SOUND Randomized Clinical Trial. JAMA Oncology 9:1557-1564, 2023.

4. Reimer T, Stachs A, Veselinovic K, et al: Axillary surgery in breast cancer: Primary results of the INSEMA trial. N Engl J Med 392:1051-1064, 2025.