Omitting Axillary Dissection Preserves Survival and Arm Function in SENOMAC

According to 5-year results from the phase 3 SENOMAC trial (NCT02240472)², presented during an oral abstract session at the 2026 ASCO Annual Meeting (May 29-June 2; Chicago, Illinois), omission of completion axillary lymph node dissection (ALND) after a positive sentinel lymph node (SLN) biopsy did not compromise overall survival (OS) in patients with breast cancer and up to 2 SLN macrometastases, while significantly reducing patient-reported arm morbidity compared with standard ALND.¹ Investigators randomized 2766 patients with primary invasive, clinically node-negative T1-3 breast cancer 1:1 to completion ALND or its omission between January 2015 and December 2021. Five-year OS was 93.4% (95% CI, 91.9%-94.9%) in the ALND group vs 94.4% (95% CI, 93.1%-95.7%) in the omission group (country-adjusted HR, 0.84; 95% CI, 0.64-1.12), meeting the trial's prespecified noninferiority margin. Arm physical function scores on the Lymph-ICF questionnaire favored omission by a clinically relevant mean difference of 6.14 points at 3 years and 5.71 points at 5 years (both P <.001)¹.

Jana de Boniface, MD, PhD, consultant breast surgeon at Capio St. Göran's Hospital and clinical professor in the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet, Stockholm, Sweden, and lead investigator of SENOMAC, spoke with Targeted Oncology^TM about the trial's design, its implications for radiotherapy planning, patient counseling around arm morbidity, and how the findings build on the existing evidence for de-escalating axillary surgery.

Targeted Oncology: To start, can you walk us through the key design and most significant findings from SENOMAC?

Jana de Boniface, MD, PhD: SENOMAC is a large, randomized, international phase 3 trial with a noninferiority design. Essentially, we wanted to find out whether a new treatment strategy is worse than the established one. We randomized 2766 patients across 5 countries between 2015 and 2021, with OS as the primary end point, which has now matured in terms of statistical power. Patients had undergone SLN biopsy with up to 2 SLN macrometastases and were randomized to completion ALND or its omission. Comparing the 2 groups, we saw no difference in OS—93.4% vs 94.4%—with a narrow confidence interval that gives us a lot of reassurance that noninferiority was met; omission is not inferior. It seems safe to conclude that patients with up to 2 macrometastases on SLN biopsy do not need completion ALND, which is fantastic news for patients.

For multidisciplinary teams, how do these findings standardize nodal radiotherapy target volumes when completion surgery is omitted?

In SENOMAC, sites applied their own international or national guidelines, so adjuvant treatment—including radiotherapy—followed standard of care at each site, and the majority of patients actually received nodal radiotherapy. That means SENOMAC can't tell us whether ALND and nodal radiotherapy can both be omitted together. We published a radiotherapy quality assessment that lays out the different target volumes used, and we're very confident that what was reported reflects what patients actually received. The quality of that reporting has been very good.

From a patient counseling standpoint, are there specific activities of daily living or functional domains where the difference between the 2 approaches is most clinically felt?

The important benefit of omitting axillary dissection is arm function. We used 2 questionnaires that look at arm function—pain, swelling, tenderness in the skin—but also daily activities like hanging up clothes, washing, or cycling. These were distributed 3 times so far, at 1, 3, and 5 years, and we'll continue at 10 years. The important finding is that patients have far fewer arm problems with less surgery, and this isn't just a temporary finding in the early postoperative period—it's consistent over time. Even at 5 years, there's still a substantial difference between the 2 groups. For patients, it's important to understand that they usually come in worried about arm lymphedema, but lymphedema is just one small part of arm morbidity. It can be the feeling of being swollen without true lymphedema, pain you have to live with, difficulty wearing certain clothes, trouble opening doors or scratching your back, or playing tennis, depending on which arm is affected. So daily activities and sports can be very much impacted.

How does this data build upon or support the existing evidence in this area?

In this area of de-escalating ALND, we now have 6 randomized trials, and SENOMAC is the largest of those. We felt we needed another trial because the earlier ones looked only at micrometastases, or a mixture of micro- and macrometastases, and they didn't include patients who needed a mastectomy or those with tumors larger than 5 cm. SENOMAC fills in those gaps. Guidelines already permitted omitting ALND after breast-conserving surgery, but now we have solid, long-term data showing this is safe for patients who require a mastectomy as well.

Watch Dr de Boniface discuss findings from SENOMAC.

REFERENCES

1. de Boniface J, Tvedskov TF, 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. Abstract LBA503. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL.

2. SENOMAC — to Assess the Safety of Omission of Axillary Lymph Node Dissection After a Positive Sentinel Node Biopsy in Patients With Breast Cancer. ClinicalTrials.gov identifier: NCT02240472. Accessed August 6, 2026. https://clinicaltrials.gov/study/NCT02240472