A Revolution in Axillary Lymph Node Biopsy – Is It Necessary for Every Patient?

In breast cancer treatment, axillary lymph node biopsy is a critical step in determining the extent of tumor spread and optimizing the treatment plan. Breast cancer tends to spread through the lymphatic system, and the axillary (underarm) lymph nodes are among its first destinations.

The sentinel lymph node is the first node to which cancer cells are likely to spread through the lymphatic system. "Sentinel" means "sentry" or "guard"; it represents the first checkpoint before cancer spreads to more distant parts of the body.

In sentinel lymph node biopsy, this first sentinel node in the lymphatic system is surgically removed and examined microscopically. If it contains no cancer, the likelihood of cancer in other axillary nodes is very low, and more extensive axillary dissection (removal of all underarm lymph nodes) is generally unnecessary.

A New Era in Breast Cancer Treatment

The INSEMA study's latest findings suggest that a standard staging procedure used in low-risk, early-stage breast cancer, sentinel lymph node biopsy (SLNB) , may not always be necessary. These findings strongly support ongoing efforts to minimize surgical interventions, reduce patients' treatment-related difficulties, and preserve oncological outcomes.

Presented on 12 December at the San Antonio Breast Cancer Symposium (SABCS) 2024 and published in The New England Journal of Medicine, the study found that omitting SLNB did not affect 5-year disease-free survival and overall survival rates. However, omission of SLNB was associated with a significant reduction in additional treatment-related problems such as lymphedema and restricted arm movement.

Key Findings of the INSEMA Study

INSEMA evaluated 5,502 women with clinically node-negative breast cancer (T1 or T2, tumor size ≤ 5 cm). They received breast-conserving surgery followed by whole-breast irradiation and were randomized to undergo or omit SLNB.

Clinically node-negative means that physical examination or imaging (ultrasound, mammography, MRI , or PET-CT) finds no evidence suspicious for cancer in the axillary lymph nodes. In this situation, sentinel lymph node biopsy can usually be performed to establish whether nodal metastases are present.

1. Patient Characteristics

   • Median Age: 62 years
   • Cancer Subtype: The great majority were hormone receptor-positive, HER2-negative
   • Tumor Size: 90% of patients had T1 disease

2. Primary Outcomes:

   • 5-Year Disease-Free Survival (DFS):
     • Without SLNB: 91.9%
     • With SLNB: 91.7% (HR: 0.91; 95% CI: 0.73-1.14)
   • 5-Year Overall Survival:
     • Without SLNB: 98.2%
     • With SLNB: 96.9%

3. Additional Findings:

   • Distant Recurrence Rate: The same in both groups at 2.7%.
   • Axillary Lymph Node Recurrence Rate: Slightly higher without SLNB (1.0% vs 0.3%), but the difference in absolute numbers was very small.
   • Treatment-Related Adverse Effects:
     • Omitting SLNB significantly reduced lymphedema (5.7% vs 1.8%), restricted arm movement (3.5% vs 2.0%), and pain with arm/shoulder movement (4.2% vs 2.0%).

The study's subgroup analysis can be seen below:

Could This Study Change Clinical Practice?

The INSEMA study adds to the evidence that sentinel lymph node biopsy can be omitted in patients with no clinical evidence of cancer spread to axillary lymph nodes at diagnosis.

Omitting SLNB may be particularly suitable for patients with tumors measuring 2 cm or less . However, SLNB remains an important staging procedure for many patients, and oncologists should make these decisions together with patients.

Omission of SLNB has long been debated and draws on earlier data. Ongoing studies such as BOOG 2013-08 and NAUTILUS could establish this approach as standard practice.

Conclusion

INSEMA is a promising step toward reducing invasive procedures in early-stage breast cancer treatment. Omitting SLNB in selected patient groups may improve comfort without compromising oncological outcomes. However, this decision requires careful individual assessment. Other large studies to be published in the future may provide stronger support for incorporating omission of SLNB into clinical practice.