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Women with breast cancer and 1-2 sentinel lymph node macrometastases can safely skip completion axillary lymph node dissection (ALND) without compromising overall survival or arm function, according to new data from the largest randomized trial of its kind to date.

The data represent the first mature analysis of the SENOMAC trial’s primary endpoint, overall survival, which was found to be noninferior in patients who skipped the procedure. While mortality data were comparable between those who received completion ALND and those who did not, patients in the omission group reported significantly better arm function.

These findings broaden the evidence base supporting omission of ALND to include populations underrepresented in earlier trials, including patients undergoing mastectomy and those with larger (T3) tumors, reported lead author Jana de Boniface, MD, PhD, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. 

“Some guidelines do not yet recommend omission of completion ALND in people with mastectomy, and I believe this will now change,” de Boniface, of Karolinska Institute and Capio St. Göran’s Hospital, Stockholm, Sweden, told Medscape Medical News.

De Boniface presented the late-breaking abstract on the SENOMAC trial at the meeting.

The previous randomized trials, ACOSOG Z0011 and AMAROS, established that many patients with limited sentinel node involvement can safely avoid completion ALND, which is associated with substantial long-term arm morbidity. 

Those findings caused a practice shift away from completion dissection; however, data have remained limited for patients undergoing mastectomy, and virtually nonexistent for those with T3 tumors, leaving areas of uncertainty. 

Earlier results of SENOMAC, published in New England Journal of Medicine and previously reported by Medscape Medical News, covered only the secondary endpoint of recurrence-free survival. That study reported noninferior 5-year recurrence-free survival, but data were not yet mature enough to report overall survival. In this new data release, the investigators reported overall survival and continued follow-up, adding patient-reported arm and quality-of-life outcomes.

Trial Design

SENOMAC randomly assigned 2766 patients, of whom 2540 were evaluable, with clinically node-negative T1 to T3 breast cancer and 1 or 2 sentinel lymph node macrometastases (greater than 2 mm) at 67 hospitals across Sweden, Denmark, Germany, Greece, and Italy, from January 2015 to December 2021. 

Patients were assigned 1:1 to completion ALND (n = 1205) or sentinel lymph node biopsy alone (n = 1335). Adjuvant treatment followed national standards of care. Nearly 90% of patients received nodal radiation. 

The median age was 61 years. Most patients had estrogen receptor-positive disease (93.6%), and 36.3% underwent mastectomy. 

Patient-reported outcomes were collected at 1, 3, and 5 years using the Lymph-ICF questionnaire and EORTC QLQ-C30 and BR23 questionnaires. The primary endpoint was overall survival.

Survival Outcomes and Arm Function

After a median follow-up of 60.1 months, 5-year overall survival was 94.4% in the omission group and 93.4% in the ALND group (hazard ratio, 0.84). Breast cancer-specific survival was 97.8% in the omission group and 97.3% with ALND, also demonstrating noninferiority. 

Deaths were distributed evenly between arms: 103 in the omission group and 100 in the ALND group, de Boniface said. Breast cancer accounted for 35 deaths in the omission group and 39 in the ALND group. 

On the Lymph-ICF arm physical function scale, where lower scores indicate fewer arm problems, the omission group reported scores about 10 points lower than the ALND group across timepoints, de Boniface said.

Mean arm symptom scores on the EORTC QLQ-BR23 questionnaire were also significantly better in the omission group than in the ALND group at 3 years and 5 years. 

These data should prompt guideline updates, de Boniface predicted, specifically for mastectomy patients.

She noted that ASCO guidelines currently allow ALND omission in mastectomy patients with tumors smaller than 5 cm who receive nodal radiation. For larger tumors, the National Comprehensive Cancer Network (NCCN) allows for ALND omission, while ASCO does not.

Confirmation, With Caveats

Monica Morrow, MD, who was the senior author of the Z0011 trial, described SENOMAC as “confirmatory,” but still valuable for the populations it added. 

“[SENOMAC] tells us that this approach can be used in mastectomy patients who will receive postmastectomy radiation therapy,” Morrow, chief of the breast service at Memorial Sloan Kettering Cancer Center in New York City, told Medscape Medical News. “It also included patients with T3 tumors who were not included in the earlier studies, and although the numbers were not large, the approach appears safe there too.” 

ALND remains indicated, she said, for patients with macrometastases in 3 or more nodes and for “the unusual T4 tumors undergoing upfront surgery.” 

Abram Recht, MD, vice chair of radiation oncology at Beth Israel Deaconess Medical Center in Boston, told Medscape Medical News that SENOMAC “adds to the considerable database” supporting ALND omission among patients with 1-2 positive sentinel nodes who undergo upfront surgery.”

Still, the necessity of ALND remains unclear among certain subgroups, including those with larger macrometastases, extranodal extension, or involvement of additional axillary nodes, Recht added.  

Morrow and Recht shared differing views on the impact of macrometastasis size. Morrow said higher-volume macrometastases do not warrant ALND, while Recht said the question remains open due to scarce data.

Radiation Remains in Question

According to Recht, one important unanswered question concerns radiation, as SENOMAC did not report how many of the 490 mastectomy patients who skipped ALND also received radiation, nor how that affected outcomes.

De Boniface added that, across the trial as a whole, 89% of patients received nodal radiation, so SENOMAC cannot address the effects of forgoing nodal radiation, too.

According to Morrow, radiation will therefore remain the norm for patients undergoing mastectomy, unless forthcoming data from ongoing trials like POSNOC (NCT02401685) change the picture.

SENOMAC was funded by the Swedish Cancer Society, the Swedish Scientific Council, the Nordic Cancer Union, and the Swedish Breast Cancer Association. De Boniface, Morrow, and Recht reported no relevant financial relationships.