Is Underarm Lymph Node Removal Necessary in Early Breast Cancer?

In breast cancer treatment, axillary lymph node biopsy is crucial for determining whether cancer has spread through the lymphatic system. Breast cancer tends to spread first to nearby axillary nodes, whose status therefore helps determine stage, prognosis and treatment. During biopsy, a small sample is taken by needle from an underarm node and examined microscopically for cancer. Positive nodes may require more extensive treatment. The information helps oncologists control disease spread and guide therapy.

Axillary biopsy and axillary lymph node dissection (ALND), the surgical removal of these nodes, have been cornerstones of breast cancer care for years. However, long-term consequences of node removal have prompted reassessment. This article discusses important SENOMAC findings that question ALND's role and reshape treatment standards.

Historical Development

Since the 1990s, ALND has been used as an alternative to sentinel node biopsy (SNB) in clinically node-negative breast cancer. Earlier trials such as ACOSOG Z0011 and AMAROS showed that SNB provides sufficient axillary staging in disease-negative individuals, and that omitting ALND does not affect overall survival or local recurrence in selected patients.

Rationale and Design

Limited statistical power and other methodological constraints in earlier trials made firm conclusions difficult. SENOMAC was designed to address this gap and establish SNB's safety in a broader population.

SENOMAC is an international randomized phase 3 noninferiority trial in clinically node-negative T1-T3 breast cancer with one or two sentinel node macrometastases. Patients were randomized to completion ALND or SNB alone. Adjuvant treatment and radiotherapy followed national guidelines.

Patient and Tumor Characteristics:

• Based in Sweden, the trial ran at 67 centers across Europe between 2015-2021 and randomized 2766 patients.
• Median follow-up was 46.8 months.
• Most received regional axillary nodal radiotherapy; only 26 received no systemic treatment.
• Approximately one third had extracapsular extension, and an average of 2 nodes were removed by SNB.
• Approximately 65% received adjuvant chemotherapy, 93% endocrine treatment and 9% HER2-targeted treatment.
• Chest-wall and regional nodal radiotherapy was given to 88%.

Results:

• Overall, 191 patients experienced recurrence or died.
• Estimated 5-year overall survival was 92.9% with SNB alone and 92.0% with dissection.
• Estimated 5-year breast cancer-specific survival was 97.1% with SNB alone and 96.6% with dissection.
• Recurrence-free survival with SNB alone was considered noninferior to dissection, with no significant difference observed.

Recurrence-Free Survival Graph

Subgroup Analyses:

• Clinically important subgroups were analyzed.
• Too few male patients were enrolled for this subgroup analysis.
• Estrogen receptor-positive, HER2-positive disease was the exception; no statistical difference between SNB alone and dissection was observed in the other subgroups.
• In the estrogen receptor-positive, HER2-positive subgroup, outcomes were better with SNB alone.

Commentary

SENOMAC has prompted reassessment of axillary surgery and opened the way to less invasive breast cancer management. Advances in radiation and adjuvant treatment raise questions about the need for this surgery. Axillary staging nevertheless remains crucial for choosing appropriate therapy. Its role requires careful consideration within multidisciplinary care aimed at improving quality of life and reducing treatment-related morbidity.