Axillary Surgery in Breast Cancer — Primary Results of the INSEMA Trial

• Published in: The New England journal of medicine Vol. 392; no. 11; pp. 1051 - 1064
• Main Authors: Reimer, Toralf, Stachs, Angrit, Veselinovic, Kristina, Kühn, Thorsten, Heil, Jörg, Polata, Silke, Marmé, Frederik, Müller, Thomas, Hildebrandt, Guido, Krug, David, Ataseven, Beyhan, Reitsamer, Roland, Ruth, Sylvia, Denkert, Carsten, Bekes, Inga, Zahm, Dirk-Michael, Thill, Marc, Golatta, Michael, Holtschmidt, Johannes, Knauer, Michael, Nekljudova, Valentina, Loibl, Sibylle, Gerber, Bernd
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 13.03.2025
• Subjects: Adult; Aged; Aged, 80 and over; Arm; Axilla - pathology; Axilla - surgery; Biopsy; Breast Cancer; Breast Cancer Lymphedema - epidemiology; Breast Cancer Lymphedema - etiology; Breast Cancer Lymphedema - prevention & control; Breast Neoplasms - diagnosis; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Breast surgery; Cancer therapies; Clinical outcomes; Death; Disease-Free Survival; Dissection; Female; Follow-Up Studies; Hematology; Humans; Incidence; Invasiveness; Kaplan-Meier Estimate; Lumpectomy; Lymph; Lymphatic Metastasis; Lymphatic system; Lymphedema; Mammography; Mastectomy, Segmental - methods; Mastectomy, Segmental - statistics & numerical data; Medical prognosis; Medical research; Middle Aged; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - prevention & control; Neoplasm Staging - adverse effects; Neoplasm Staging - methods; Oncology; Patients; Prospective Studies; Quality of life; Questionnaires; Radiation therapy; Sentinel Lymph Node Biopsy - adverse effects; Sentinel Lymph Node Biopsy - methods; Sentinel Lymph Node Biopsy - statistics & numerical data; Statistical analysis; Surgery; Surgery General; Surgical outcomes; Survival; Treatments in Oncology; Ultrasonic imaging; Young Adult; Austria
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa2412063

Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear. In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271. A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio. The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group). The median follow-up was 73.6 months. The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin. The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%). The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy. In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years. (Funded by the German Cancer Aid; INSEMA ClinicalTrials.gov number, NCT02466737.).