The INSEMA trial, a prospective, randomized, noninferiority study, reveals that omitting axillary surgery in patients with clinically node-negative, early-stage breast cancer does not compromise survival outcomes. This 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 study, presented at the San Antonio Breast Cancer Symposium and published in The New England Journal of Medicine, suggests 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.
Study Design and Patient Population
The INSEMA trial enrolled 5,502 patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size ≤ 5 cm) scheduled for breast-conserving surgery. Conducted in Germany and Austria between 2015 and 2019, patients were randomly assigned in a 1:4 ratio to either the surgery-omission group (no axillary surgery) or the surgery group (sentinel lymph node biopsy, SLNB). 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, with a median follow-up of 73.6 months.
Key Findings on Survival and Recurrence
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.
Impact on Quality of Life
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 improvement in quality of life is a significant benefit of the de-escalation approach.
Implications for Clinical Practice
The INSEMA trial, along with previous studies like the SOUND trial, supports the omission of axillary surgery in select patients with early-stage breast cancer. According to Dr. Toralf Reimer of the University of Rostock, Germany, this de-escalation concept may be suitable for patients 50 years of age or older who present with low-risk (grade 1 or 2), HR-positive, HER2-negative invasive breast cancer and clinical T1 tumors.
Dr. Monica Morrow of Memorial Sloan Kettering Cancer Center emphasizes the importance of multidisciplinary consideration when de-escalating any therapeutic approach. She notes that the INSEMA and SOUND data provide a strong foundation for incorporating the elimination of sentinel lymph node biopsy into practice, particularly for patients with grade 1 or 2, cT1 tumors.
Considerations for Patient Selection
While the INSEMA trial provides valuable insights, it's important to consider patient-specific factors when deciding whether to omit axillary surgery. Factors such as tumor size, grade, hormone receptor status, and HER2 status should be taken into account. Additionally, the role of preoperative imaging and the need for shared decision-making with patients and the multidisciplinary team are critical when determining who can safely omit sentinel node biopsy without compromising their care.
