BACKGROUND AND PURPOSE:

• Reimer et al. (NEJM, 2024) report on whether complete omission of axillary surgery in early-stage breast cancer treated with breast-conserving surgery is noninferior to more invasive options

METHODS:

• Prospective, multicentered, randomized, noninferiority trial
  • INSEMA (Intergroup-Sentinel-Mamma)
  • Comparison of axillary sentinel lymph node biopsy versus no axillary surgery
  • 142 sites in Germany | 9 sites in Austria
• Participants
  • Patients with clinically node-negative invasive breast cancer | Staged as T1 or T2 (tumor size ≤5 cm) | Scheduled to undergo breast-conserving surgery
• Interventions
  • Surgery omission group: treatment without axillary surgery
  • Surgery group: sentinel-lymph-node biopsy 
    • Further randomization for those in this group with pathological sentinel-node–positive status to dissection or no dissection
    • Results of second randomization are not reported here
• Study design
  • Analyses were conducted per-protocol
  • Needed for noninferiority
    • 5-year invasive disease–free survival rate ≥85% AND
    • Upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) for invasive disease or death had to be below 1.271
• Primary outcome
  • Invasive disease-free survival

RESULTS:

• Surgery omission group: 962 patients | Surgery group: 3896 patients
  • Median follow-up: 73.6 months
• Surgery omission was noninferior to surgery for estimated 5-year invasive disease–free survival
  • Surgery omission: 91.9% (95% CI, 89.9 to 93.5) | Surgery: 91.7% (95% CI, 90.8 to 92.6)
  • HR 0.91 (95% CI, 0.73 to 1.14)
• Estimated 5-year overall survival rate
  • Surgery omission: 98.2% (95% CI, 97.1 to 98.9)
  • Surgery: 96.9% (95% CI, 96.3 to 97.5)
• Subgroup analysis of tumor size resulted in larger T2 confidence intervals for 5-year invasive disease–free survival
  • T2: HR 0.71 (95% CI, 0.39 to 1.32)
  • T1: HR 0.95 (95% CI, 0.75 to 1.20)
• Long term safety analysis favored surgery omission vs surgery group
  • Lymphedema: 1.8% vs. 5.7%
  • Restriction of arm or shoulder mobility: 2.0% vs. 3.5%
  • Pain with arm or shoulder movement: 2.0% vs. 4.2%

CONCLUSION:

• Omitting axillary surgery for patients with clinically node-negative, T1 or T2 invasive breast cancer was noninferior to sentinel-lymph-node biopsy after a median of 6 years of follow-up
• The authors state

Our trial shows that the omission of axillary-sentinel-lymph-node biopsy does not compromise survival in patients with early-stage, cN0 breast cancer who plan to undergo primary breast-conserving surgery

This de-escalation concept may be suitable for patients 50 years of age or older who present with low-risk (grade G1 or G2), HR-positive, HER2-negative invasive breast cancer and clinical T1 tumors

Learn More – Primary Sources:

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