Omitting axillary surgery may be an option for some patients with early-stage breast cancer, according to a study reported by Reimer et al in The New England Journal of Medicine. Previous studies, such as the SOUND trial, have indicated that avoiding an axillary procedure in patients with small breast cancer (up to 2 cm) is not inferior to sentinel lymph node biopsy (SLNB).
The main goal of the INSEMA study—one of four ongoing de-escalation trials—was to establish that the complete omission of axillary surgery does not compromise invasive disease–free survival in patients with early-stage breast cancer who undergo breast-conserving surgery. In addition, secondary outcomes from the study showed that patients who did not undergo SLNB reported fewer arm symptoms and better functioning, indicating a significant improvement in quality of life.
Study Protocol
This prospective, randomized, noninferiority trial enrolled 5,502 patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size ≤ 5 cm) who were scheduled for breast-conserving surgery. Patients were randomly assigned 1:4 into two groups: the surgery-omission group, which did not undergo axillary surgery, and the surgery group, which underwent SLNB. Recruitment for the trial was conducted in Germany and Austria between 2015 and 2019.
The primary endpoint was 5-year invasive disease–free survival, with a noninferiority margin set at 85% and an upper hazard ratio (HR) limit of 1.271. Secondary endpoints included axillary recurrence rates, overall survival, and quality-of-life outcomes. The per-protocol analysis included 4,858 patients, and the median follow-up was 73.6 months.
Key Findings
The study revealed that omitting axillary surgery in patients with clinically node-negative, early-stage breast cancer did not compromise survival outcomes. The 5-year invasive disease–free survival rate was 91.9% (95% confidence interval [CI] = 89.9–93.5) in the surgery-omission group compared to 91.7% (95% CI = 90.8–92.6) in the surgery group. The HR of 0.91 (95% CI = 0.73–1.14) confirmed noninferiority, staying within the prespecified margin of 1.271. Axillary recurrence was slightly higher in the surgery-omission group (1.0% vs 0.3%), while mortality was lower (1.4% vs 2.4%), though this was not the trial’s primary endpoint. Patients in the surgery-omission group reported fewer complications, including a significantly lower incidence of lymphedema and better arm mobility with less pain during movement.
This de-escalation approach may be particularly suitable for patients aged 50 years or older, with grade 1 to 2 tumors, a hormone receptor–positive/HER2-negative disease subtype, and a preoperative tumor size of up to 2 cm. The findings suggest that omitting axillary surgery could be a viable option for select patients, reducing unnecessary procedures while maintaining excellent survival outcomes and improved quality of life.
Dr. Reimer, of University of Rostock, Germany, is the corresponding author for The New England Journal of Medicine article.
Disclosure: This study was funded by the German Cancer Aid. For full disclosures of the study authors, visit www.nejm.org.
