Sentinel Lymph Node Biopsy in the Setting of Neoadjuvant Chemotherapy (NAC)

• Although neoadjuvant chemotherapy (NAC):
  • Can decrease the size of a primary tumor to allow for breast conservation, eliminate nodal metastasis in some patients, and provide prognostic information:
    • The optimal timing of sentinel lymph node biopsy (SLNB) for patients treated with NAC has been controversial
• Clinical staging of the axilla with SLNB:
  • Is feasible both before and after chemotherapy
• SLNB prior to NAC:
  • May be a more accurate approach than after NAC
  • Chemotherapy:
    • May alter lymphatic drainage through fibrosis of lymphatic channels:
      • Decreasing the accuracy of SLNB
  • SLNB before NAC has a lower false negative rate and provides more accurate staging:
    • Which could determine radiation fields
  • Unfortunately, SLNB prior to NAC:
    • Requires an additional operation
    • Could delay the initiation of chemotherapy
    • Fails to decrease the rate of ALND
    • It also given by the effect of chemotherapy on axillary metastasis
• These concerns have led to interest in performing SLNB after NAC
• Several recent prospective trials have examined the accuracy of SLNB after NAC:
  • The American College of Surgeons Oncology Group (ACOSOG) Z1071:
    • Enrolled women with T0 to T4, N1 to N2 clinical disease:
      • Who underwent neoadjuvant chemotherapy
    • All patients underwent pre-NAC axillary needle biopsy
    • Forty-one percent of patients had a:
      • Pathologic complete response in the axilla
    • After chemotherapy:
      • Patients underwent both SLNB and ALND
    • A sentinel lymph node could not be identified:
      • In 7% of patients
    • The overall false negative rate was 13%:
      • Which did not meet the preset target of 10%
    • The false negative rate was 21% in patients with two or fewer sentinel lymph nodes identified:
      • But dropped to 9.1%:
        • When greater than three sentinel lymph nodes were sampled
  • In the Sentinel Lymph Node Biopsy in Patients with Breast Cancer Before and After Neoadjuvant Chemotherapy (SENTINA) trial:
    • 1,022 patients underwent SLNB before NAC:
      • With a detection rate of 99%
    • For patients who were evaluated after NAC and converted from cN+ to ycN0:
      • The sentinel lymph node detection rate was only 80%:
        • With a false negative rate of 14.2%
    • As seen in ACOSOG Z1071:
      • The false negative rate:
        • Was much higher in patients with only one node removed (24%):
          • Than in those with three or more sentinel nodes removed (7%)
    • The false negative rate was also improved:
      • By the use of radiocolloid and blue dye together:
        • Compared with blue dye alone:
          • False negative rate of 9% versus 16%
  • The Sentinel Node Biopsy following NeoAdjuvant Chemotherapy (SN FNAC) study:
    • Enrolled patients with T0 to T3 with N1 to N2 biopsy-proven breast cancer treated with NAC
    • Following chemotherapy, patients underwent clinical and ultrasound examination followed by SLNB and completion ALND
    • The overall post-NAC SLNB false negative rate was:
      • 8% in 153 patients
    • When only one sentinel lymph node was evaluated:
      • The false negative rate was again unacceptably high:
        • At 20%
• On the basis of these three trials:
  • Resecting only one sentinel node:
    • Is associated with an unacceptably high false negative rate
  • The false negative rate after NAC may be lowered with the use of:
    • Dual tracers and resecting three or more sentinel nodes
    • Placing clips in positive lymph nodes before chemotherapy:
      • Decreases the false negative rate:
        • If the clipped node is then resected during SLNB
  • The sentinel lymph node identification rate after NAC:
    • Is significantly improved with increased surgeon experience:
      • Suggesting that a learning curve is needed to obtain accurate SLNB after NAC
• SLNB after NAC:
  • Has the potential to decrease the number of women who receive ALND
• A study of 288 prospectively identified clinically node-positive patients:
  • Reported that 132 became clinically node negative after NAC
  • The clinically node-negative patients were then eligible for SLNB:
    • 48% had negative sentinel lymph nodes and were able to avoid an ALND
• Current ASCO recommendations state that:
  • SLNB should be offered to patients who have received preoperative neoadjuvant systemic therapy and have clinically negative lymph nodes:
    • However, no large studies have examined local recurrence rates or survival:
      • When ALND is omitted in patients who convert from node positive to node negative after NAC
    • The safety of avoiding ALND in these patients:
      • Has not been demonstrated
• The National Surgical Adjuvant Breast and Bowel Project (NSABP) B51 and Alliance A011202 are two sister studies:
  • Examining the role of SLNB, ALND, and nodal radiation in patients who receive NAC
  • The results of these trials will help identify patients who can safely avoid ALND after NAC

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