For a stage I‑III breast cancer patient with isolated tumor cells in the sentinel lymph node after neoadjuvant chemotherapy, is completion axillary lymph‑node dissection required?

Completion Axillary Lymph Node Dissection for Isolated Tumor Cells After Neoadjuvant Chemotherapy

Completion axillary lymph node dissection is NOT routinely required for patients with isolated tumor cells (ypN0i+) in sentinel lymph nodes after neoadjuvant chemotherapy, as the ICARO study demonstrates low nodal burden (only 5% macrometastases at ALND) and rare axillary recurrence (2% at 3 years) when ALND is omitted in appropriately selected patients. 1

Evidence from the ICARO Study (2025)

The most recent and highest-quality evidence comes from the multicenter OPBC-05/ICARO cohort study, which analyzed 583 patients with stage I-III breast cancer who had isolated tumor cells in sentinel lymph nodes after neoadjuvant chemotherapy 1:

• Only 30% of patients who underwent completion ALND had any additional positive nodes, and critically, only 5% had macrometastases 1
• The 3-year axillary recurrence rate was 2% (95% CI, 0.95-3.6%) with no statistical difference between patients treated with or without ALND 1
• The 3-year rate of any invasive recurrence was 11% (95% CI, 8-14%), again with no difference by type of axillary surgery 1

Clinical Decision Algorithm

Patients Who May Safely Avoid ALND:

• Isolated tumor cells detected on final pathology (not frozen section) 1
• Clinical stage N0-N1 disease at diagnosis 1
• Absence of lymphovascular invasion 1
• Receipt of appropriate adjuvant radiation therapy (chest wall and nodal fields as indicated) 1

Patients Who May Still Require ALND:

• ITCs detected on intraoperative frozen section (associated with higher rates of completion ALND in the ICARO cohort: 62% vs 8%, P<0.001) 1
• Clinical N2/N3 disease at presentation (17% underwent ALND vs 7% who did not, P<0.001) 1
• Presence of lymphovascular invasion (38% vs 24%, P<0.001) 1

Important Caveats and Contradictory Evidence

A critical caveat exists: An earlier 2018 study from Memorial Sloan Kettering found that 64% of patients with micrometastases (not just ITCs) after neoadjuvant chemotherapy had additional positive nodes at ALND 2. However, this study included micrometastases, which represent a higher disease burden than isolated tumor cells.

The pathologic definition matters: Isolated tumor cells after neoadjuvant chemotherapy are predictors of worse survival compared to truly node-negative disease, and specimens with ITCs should not be designated as having pathological complete response 3. The size of metastatic deposits should be measured as the entire area partly involved by tumor, not just the largest cluster 3.

Historical Context and Evolution of Practice

Previous guidelines recommended completion ALND for node-positive patients after neoadjuvant therapy 3:

• The ACOSOG Z1071 trial showed a 12.6% false-negative rate for sentinel node biopsy after neoadjuvant chemotherapy when patients had initially positive nodes 4
• ASCO guidelines from 2014 noted that for patients with metastatic nodes before neoadjuvant chemotherapy, the false-negative rate with sentinel node biopsy after treatment may range from 10-30% 3
• Level I/II dissection was recommended when patients were proven node-positive before neoadjuvant therapy (category 2B) 3

However, the ICARO study specifically addresses the subset of patients who achieve near-complete nodal response (ypN0i+), demonstrating that this population has substantially lower residual disease burden than previously appreciated 1.

Radiation Therapy Considerations

The NSABP B-51 trial (2025) provides additional context: regional nodal irradiation did not improve outcomes in patients who achieved ypN0 status after neoadjuvant chemotherapy 5. While this study excluded patients with isolated tumor cells, it reinforces that excellent locoregional control can be achieved without aggressive surgical intervention in patients with minimal residual nodal disease 5.

Practical Implementation

For patients with ypN0i+ after neoadjuvant chemotherapy:

• Omission of completion ALND is reasonable in patients with favorable characteristics (cN0-N1 at diagnosis, no lymphovascular invasion, ITCs detected on final pathology only) 1
• Adjuvant radiation therapy to chest wall and regional nodes should be administered per standard protocols 1
• Close multidisciplinary communication between surgery, pathology, and radiation oncology is essential 3
• The mean number of sentinel nodes with ITCs in the ICARO study was 1.2, suggesting limited disease burden 1