Omitting ALND Shows Non-Inferiority, Fewer Arm-Related Complications in Breast Cancer

Among patients with breast cancer and macrometastases, those who omitted axillary lymph node dissection (ALND) experienced non-inferior survival outcomes and significantly less arm-related complications compared with those who completed ALND.^1,2 These result from the phase 3 SENOMAC trial (NCT02240472) were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

At a median follow-up of 60.1 months, the 5-year overall survival (OS) rate was 93.4% (95% CI, 91.9%-94.9%) in the completion ALND group vs 94.4% (95% CI, 93.1%-95.7%) in the omission group, with a hazard ratio of 0.89 (95% CI, 0.67-1.17). Non-inferiority was confirmed (P < .001). Five-year breast cancer-specific survival was 97.2% in the ALND group vs 97.9% in the omission group.

Background and Study Rationale

For decades, finding cancer in sentinel lymph nodes during a sentinel lymph node biopsy (SLNB) has typically prompted surgeons to perform a completion ALND to remove additional lymph nodes from the axilla. While the procedure improves staging information, it has long been associated with significant morbidity, including pain, numbness, limited arm mobility, and lymphedema.

Prior trials had raised the possibility that ALND could safely be omitted in some patients, but those studies lacked sufficient statistical power and excluded important subgroups, most notably patients undergoing mastectomy or those with larger primary tumors exceeding 5 cm in diameter. SENOMAC was designed to fill those gaps.

“After previous trials, it was unclear whether the omission of ALND could also be offered to patients receiving a mastectomy or those with larger tumors,” said lead study author Jana de Boniface, MD, PhD, from the Department of Surgery at Capio St. Göran's Hospital and the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. “The key finding is that more axillary surgery in itself does not improve survival in these patients. This is extremely important because it means that axillary surgery should be seen as a diagnostic instrument, not a therapeutic tool.”

Study Design and Patient Characteristics

SENOMAC enrolled 2540 patients across Sweden, Denmark, Germany, Greece, and Italy between February 2015 and December 2021. Eligible patients had primary breast cancer of any size, no abnormal lymph nodes on palpation, and 1 to 2 sentinel lymph node macrometastases greater than 2 mm in diameter. Both breast-conserving surgery and mastectomy were permitted. The per-protocol population included 919 patients (36%) who underwent mastectomy and 147 patients (6%) with tumors larger than 5 cm — two subgroups historically excluded from prior trials. The median age of participants was 61 years, 93.6% had estrogen receptor-positive tumors, and enrollment was led by Sweden (n =1553) and Denmark (n =803), with additional sites in Germany ( n = 86), Greece (n = 52), and Italy (n = 46).

Following a positive SLNB showing up to 2 macrometastases, patients were randomized 1:1 to completion ALND (n = 1205) or omission of completion ALND (n = 1335). Both groups received adjuvant treatment according to current standards of care, which commonly included radiation therapy to the regional lymph nodes; 88% of patients received locoregional radiotherapy. Of note, additional cancer was identified on completion ALND in 34.3% of patients who underwent the procedure, underscoring the high rate of residual nodal disease that is effectively left untreated in the omission group, with no apparent survival consequence.

Arm Function and Quality of Life

SENOMAC captured patient-reported outcomes using two validated instruments: the Lymph-ICF questionnaire assessing lymphedema-related arm function, and the EORTC QLQ-BR23 questionnaire assessing breast cancer-specific arm symptoms. These were administered at 1, 3, and 5 years post-randomization. Questionnaire response rates were 83% at 1 and 3 years and 81% at 5 years.

On the Lymph-ICF scale (0-100, with higher scores indicating greater impairment), patients in the omission group reported consistently better arm function at 1 year (mean score difference, 10.64), 3 years (mean score difference, 10.73), and 5 years (mean score difference, 10.75). On the EORTC QLQ-BR23 arm symptoms subscale, the cALND group began with notably higher arm symptom scores at baseline (approximately 24) that increased further at year 1 (approximately 25) before declining toward year 5 (approximately 20), while the omission group maintained consistently lower and stable symptom scores throughout—approximately 14 at baseline and approximately 10 at year 5—with fewer arm problems reported in the omission group at 1 year (mean score difference, 10.90), 3 years (9.86), and 5 years (10.02).

Arm physical function scores told a similarly consistent story. The omission group maintained low, stable physical function impairment scores throughout all follow-up time points (approximately 10 to 12 across years 1 through 5), while the cALND group started with markedly higher impairment scores of approximately 20 at baseline and remained persistently elevated at approximately 21 through year 5, with no meaningful recovery over time. The clinical significance of this difference was stark: 12.6% of patients in the completion ALND group reported severe or very severe problems with arm physical function at 5 years, compared with just 3.6% in the omission group, representing a greater than threefold difference (P < .001).

Global health-related quality of life scores also consistently favored the omission group across all time points. At baseline, the cALND group started at a notably lower global health score of approximately 65 compared with approximately 68 in the omission group. While both groups improved over the follow-up period, the omission group maintained higher scores throughout—reaching approximately 74 at years 3 and 5 compared with approximately 71 to 72 in the cALND group—with the gap between the two arms persisting through the full 5-year follow-up period.

“Lymphedema can be a devastating quality-of-life issue that alters a woman's mobility, appearance, and self-esteem long after breast cancer treatment is complete. This rigorous, large-scale trial proves that we can safely skip invasive axillary node dissection in patients with limited nodal disease, and that by avoiding this additional surgery, we can drastically reduce long-term arm complications and improve arm function for breast cancer patients even years out from their diagnosis. These findings have the potential to simplify surgical management and meaningfully impact breast cancer survivorship for women throughout the world,” said Jane Lowe Meisel, MD, FASCO, a medical oncologist at Winship Cancer Institute of Emory University and an ASCO Expert in breast cancer.

The SENOMAC investigators are now launching SENOMAC-ULTRA, a new randomized trial comparing ALND against targeted axillary dissection—a procedure that removes significantly fewer lymph nodes than a full ALND—in patients with known axillary spread, continuing to push the boundaries of surgical de-escalation in breast cancer management.

References

1. de Boniface J, Filtenborg Tvedskov T, Rydén 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. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29–June 2, 2026; Chicago, IL.
2. American Society of Clinical Oncology. Some breast cancer patients with sentinel lymph node spread can safely skip axillary lymph node dissection. ASCO press release. May 30, 2026. Accessed May 30, 2026. https://www.asco.org/about-asco/press-center/news-releases/2026/senomac-trial