Targeted axillary dissection after neoadjuvant therapy in breast cancer

The presence of nodal metastases is an important prognostic factor used to direct locoregional and systemic therapies. The use of neoadjuvant therapy has been shown to eliminate nodal metastases in between 40 and 75 per cent of patients1,2. Consequently, this provides the opportunity for a significant proportion of patients undergoing neoadjuvant therapy to avoid axillary lymph node dissection (ALND). However, there has been reluctance to perform sentinel node biopsy (SNB) on completion of neoadjuvant therapy in patients with histologically confirmed axillary metastases owing to raised falsenegative rates (FNRs) in excess of 10 per cent, even if dual localization techniques and more than two sentinel nodes are excised1,3. A novel approach to addressing this issue has now emerged from several units in the USA and Europe, who have developed the concept of ‘targeted excision’ of suspicious axillary lymph nodes. This procedure involves patients scheduled to receive neoadjuvant therapy undergoing axillary staging using ultrasound imaging. Suspicious lymph nodes identified on ultrasonography are subjected to core biopsy and at that point (or on pathological confirmation) a marker clip is placed in the node by the radiologist. Patients complete neoadjuvant therapy and then undergo repeat axillary staging using ultrasound imaging. At this point, the marker clipped node is identified and a surgically localizable technique applied to guide intraoperative excision. Caudle and colleagues4 carried out a prospective evaluation of 208 patients with node-positive disease undergoing neoadjuvant therapy. Fine-needle aspiration of the most abnormal appearing node was performed and pathological evaluation carried out. If metastases were identified, a clip was placed in the biopsied node. After completion of neoadjuvant therapy, patients underwent repeat axillary ultrasonography, and an 125I-labelled radioactive seed (125I seed) was introduced under ultrasound guidance into the clipped node between 1 and 5 days before surgery. A total of 118 patients then underwent SNB using the dual technique with radioisotope and blue dye, followed by targeted axillary dissection of the 125I-containing node and formal ALND. The FNR for SNB was 10⋅1 (95 per cent c.i. 4⋅2 to 19⋅8) per cent and that for excision of the clipped node 4⋅2 (1⋅4 to 9⋅5) per cent; combined evaluation resulted in a FNR of only 1⋅4 (0⋅0 to 7⋅3) per cent. The clipped node was not identified as the sentinel node in 23 per cent of patients and this was significantly associated with more than four suspicious nodes (P = 0⋅004). Diego and co-workers5 assessed a small cohort of 22 patients who became radiologically node-negative after neoadjuvant therapy. These patients underwent targeted axillary dissection of the 125I seed and concurrent SNB, but not ALND. The 125I seed-containing node was not the sentinel node in two of 22 patients. Donker et al.6 coined the term MARI procedure (marking axillary lymph nodes with radioactive iodine seeds). They evaluated 103 patients undergoing neoadjuvant therapy who had an 125I seed placed into a node with proven metastasis (up to 31 weeks before surgery) followed by ALND. The FNR of the MARI procedure was 7 (95 per cent c.i. 2 to 16) per cent. When the MARI node was positive, additional nodes with macrometastasis were identified in 70 per cent of patients. The high FNR in the axilla after neoadjuvant therapy is not attributed solely to low sentinel node identification rates, as demonstrated by Boughey and colleagues1 who reported an identification rate of 92⋅7 (95 per cent c.i. 90⋅5 to 94⋅5) per cent, but a FNR of 12⋅6 (9⋅9 to 16⋅1) per cent. The use of targeted axillary dissection indicates that there is a lack of concordance between the sentinel node and metastatically involved nodes. This is likely explained by the advanced presentation of disease to the axilla and the subsequent response to neoadjuvant therapy with distortion of axillary drainage pathways. The use of targeted axillary dissection as an adjunct in this challenging situation provides a unique technique to ensure with confidence the absence of additional axillary disease, in the event that the excised, targeted node is free from metastatic disease on completion of neoadjuvant therapy. Such practice would allow patients who experience an excellent response to neoadjuvant therapy to avoid unnecessary ALND with its associated morbidity.