Management of the Axilla in Clinically Node-Positive Patients Following Neoadjuvant Chemotherapy (NAC)

• Management of the axilla in clinically node-positive (cN1) patients following neoadjuvant chemotherapy (NAC) has evolved significantly over the past several years:
  • Historically:
    • The use of sentinel lymph node biopsy (SLNB) in initially node-positive patients after NAC was avoided because available data demonstrated :
      • False-negative rates approaching 25%:
        • Therefore, all patients were treated with axillary lymph node dissection post-NAC regardless of response to treatment.
  • Three recently published prospective studies evaluated the accuracy of sentinel node biopsy following NAC in patients presenting with node-positive disease:
    • Among 525 patients enrolled in the ACOSOG Z1071 trial with at least two sentinel nodes removed:
      • The false-negative rate was 12.6%>
        • However:
          • The false-negative rate was reduced to:
            • 10.8% when the SNB was performed with dual mapping (radioactive tracer and blue dye)
            • 9.1% when 3 or more sentinel nodes were removed.
    • Similarly, the overall false-negative rate among 226 clinically node-positive patients enrolled in the SENTinel NeoAdjuvant (SENTINA) prospective study:
      • Was 14.2%:
        • Which decreased to 8.6% with the use of dual mapping
        • 7.3% when 3 or more sentinel nodes were retrieved.
    • Although a false-negative rate of less than 10% is acceptable in the adjuvant setting:
      • Additional methods to decrease false-negative rates in this population are of clinical interest:
        • As the long-term consequences of leaving behind potentially “chemotherapy-resistant” cells are unknown:
          • One method to potentially improve the accuracy of SNB in this setting is:
            • To clip the cN1 positive node:
              • Then post-NAC localize the node and ensure removal of the clipped positive node at the time of SNB.
              • In a subset analysis of patients enrolled in the ACOSOG Z1071 trial with cN1 disease and at least two sentinel nodes removed, the false-negative rate of sentinel node biopsy was 6.8% when the clipped node was one of the sentinel nodes, 19% when the clipped node was found in the axillary dissection specimen, and identified, compared to 14.3% when the clip was placed but location was unknown.
              • The false-negative rate was 13.4% when no clip was placed.
      • Caudle et al. recently reviewed their experience with SNB and retrieval of the clipped node, also known as targeted axillary dissection, in clinically node-positive patients receiving NAC:
        • Among 85 patients who underwent targeted axillary dissection followed by axillary lymph node dissection, the false-negative rate was 2.0% compared to 10.6% for SNB alone in this cohort (p=0.13).
        • Importantly however, the mean number of sentinel lymph nodes removed in this cohort was 2.7 and dual tracer mapping was only used in 55% of the patients.
          • Further study of this technique is ongoing.
      • Other methods to minimize false-negative rates include documentation of treatment effect in the node:
        • Which may also serve as a surrogate that the original positive node(s) has/have been retrieved.
      • Although controversy exists as to the best method to evaluate the axilla post-NAC in patients presenting with node-positive disease:
        • SNB with localization of the clipped node and/or SNB with dual mapping and retrieval of 3 or more sentinel nodes are both acceptable approaches to the axilla following NAC.

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