Evolution of Axillary Management in Breast Cancer Therapy: A Focus on De-escalation and Escalation Strategies

Local Therapy of the Axilla

Scenario 1: cN0 and Upfront Surgery

The shift from ALND to SLNB in clinically node-negative (cN0) patients represents a significant de-escalation in breast cancer therapy. This change is driven by the desire to reduce morbidity associated with ALND, such as lymphedema, loss of sensation, pain, and reduced mobility. SLNB has become a widely accepted method for nodal staging in cN0 patients, supported by guidelines suggesting that SLNB may not be necessary for certain patient groups, such as those over 70 years with ER+/HER2-negative early-stage breast cancer.

Scenario 2: Treatment of the Axilla in cN0/pN1(sn)

The management of the axilla in patients with a positive sentinel node (pN1(sn)) has evolved, with studies questioning the necessity of completion ALND in patients with 1-2 positive SLNs. The ACOSOG Z0011 and AMAROS trials have provided evidence supporting the omission of ALND in favor of axillary radiotherapy, highlighting similar outcomes in terms of overall survival (OS) and disease-free survival (DFS) between treatment arms.

Scenario 3: cN0 → ycN0

The timing of SLNB in patients undergoing primary systemic therapy (PST) has been investigated, with trials like GANEA-2 and SENTINA showing the feasibility of performing SLNB after PST. This approach allows for an individualized post-neoadjuvant strategy based on the response to treatment in both the primary tumor and regional nodes.

Scenario 4: cN0 → ypN1

The optimal management of the axilla in patients with residual nodal metastasis after PST remains a topic of debate. While ALND is recommended for patients with macro- and micrometastasis in sentinel nodes, the decision to perform ALND in the presence of isolated tumor cells (ITCs) is made on an individual basis.

Scenario 5: cN+ before PST

The management of the axilla in clinically node-positive patients undergoing PST is highly controversial. The potential for surgical de-escalation in patients achieving axillary pathological complete response (pCR) is weighed against the risk of increased recurrence rates. Ongoing trials aim to clarify the optimal surgical staging strategy and the role of radiotherapy in this setting.

Conclusion

The management of the axilla in breast cancer therapy has undergone significant changes, with a shift towards less invasive procedures and a focus on individualized treatment strategies. The ongoing debate between de-escalation and escalation strategies highlights the complexity of axillary management and the need for further research to optimize patient outcomes.