How should the axilla be managed in breast cancer patients in the era of de-escalation?

Axillary Management in Breast Cancer: The Era of De-escalation

In the era of de-escalation, axillary management in breast cancer should be tailored to tumor biology, nodal burden, and response to therapy, with minimization or omission of axillary surgery in carefully selected patients to reduce morbidity without compromising oncologic outcomes. 1

Principles of De-escalation in Axillary Management

• De-escalation aims to minimize morbidity (lymphedema, pain, stiffness, sensory loss) while maintaining excellent oncologic outcomes 1
• The goal is to individualize interventions based on pathology, tumor burden, and systemic therapy response 2, 3
• Multidisciplinary team approach is essential for optimal decision-making 1

Management of Clinically Node-Negative (cN0) Patients

Who Can Avoid Axillary Surgery Upfront?

• Low-risk patients meeting specific criteria may avoid axillary surgery altogether 1, 4:
  • Age ≥50 years, grade 1-2, HR+/HER2-, T1-T2 tumors (≤5 cm) with breast conservation planned (INSEMA trial criteria) 4, 5
  • Predominantly postmenopausal ER+/HER2-, T1 tumors (≤2 cm) with breast conservation planned (SOUND trial criteria) 4, 5
  • Clinically node-negative by exam and axillary ultrasound with no suspicious nodes 1

Management Options for cN0 Patients

• Sentinel lymph node biopsy (SLNB) remains the standard of care for most cN0 patients 1
• Axillary lymph node dissection (ALND) is rarely indicated in cN0 patients 1
• No axillary surgery may be considered in very low-risk cohorts per trial criteria 4, 5
• Preoperative axillary ultrasound can help identify patients with unsuspected extensive nodal disease 1

Management of Node-Positive Patients

Patients with Limited Nodal Disease (1-2 Positive SLNs)

• ALND can be safely omitted in patients with 1-2 positive SLNs who are undergoing breast-conserving surgery with planned whole breast radiation 1
• This approach is supported by the Z0011 trial, which showed no difference in survival between ALND and no ALND groups at 9.3 years median follow-up 1
• Regional nodal irradiation (RNI) is a valid alternative to ALND in patients with positive SLNs 1, 3

After Neoadjuvant Systemic Therapy (NAST)

• For initially cN1 patients who convert to ypN0 after NAST:
  • SLNB alone may be sufficient without further axillary treatment 1, 3
  • Omission of RNI can be considered in selected patients based on the NSABP B-51/RTOG 1304 trial 3
• For initially cN2/N3 patients:
  • Most do not achieve axillary pathologic complete response (pCR) and may still need ALND 1, 3
  • Selected patients achieving ypN0 may be managed with SLNB alone in trial settings 2, 3

After Neoadjuvant Endocrine Therapy (NET)

• Management is evolving with opportunities for de-escalation in selected cases 6
• In clinically node-negative (cN0) patients selected for NET, over 90% have fewer than three positive nodes at surgery 6
• No survival difference has been observed between SLNB and ALND in patients with limited residual nodal disease after NET 6

Role of Axillary Radiotherapy

• Regional nodal irradiation (RNI) is important for patients with residual nodal disease after neoadjuvant therapy (ypN+) 3
• For patients converting to ypN0 after neoadjuvant therapy, selective omission of RNI may be appropriate in some groups 3
• Axillary radiation is a valid alternative to ALND in patients with positive SLNs 1, 3

Practical Algorithm for Axillary Management

For Upfront Surgery (cN0, ultrasound-negative)

• Low-risk patients per INSEMA/SOUND criteria → consider no axillary surgery 4, 5
• Otherwise → SLNB; ALND only if heavy nodal burden or management-changing 1

After Neoadjuvant Systemic Therapy

• Initially cN1 → ypN0: consider omitting RNI; discuss SLNB-only approach 3
• Initially cN2/3: if ypN0 in a trial-like setting, SLNB±RNI may suffice; otherwise ALND 1, 2

Common Pitfalls and Caveats

• Preoperative axillary ultrasound has variable sensitivity (52-90%) and should not be the sole determinant for axillary management 1
• After neoadjuvant therapy, SLNB has better accuracy when using dual tracer technique and removing at least 3 sentinel nodes 1
• Patients with aggressive tumor phenotypes (triple-negative or HER2+) achieving pCR may be candidates for more de-escalated approaches, but this is still under investigation 3, 4
• The management of the axilla after neoadjuvant endocrine therapy is less well-established than after chemotherapy 6