Abstract CS01-1: The role of pathological staging of the axilla and sentinel lymph node biopsy before versus after neoadjuvant chemotherapy
Authors: Newman LA 
Published: August 2014

Neoadjuvant (neo) chemotherapy (CTX) is standard of care for managing pts that present with locally advanced/inoperable breast cancer. This strategy is also routinely offered to women whose cancers are resectable but where primary tumor downstaging is expected to improve lumpectomy eligibility and cosmesis. In the latter scenario it must be clear that CTX is an indicated component of the multidisciplinary care, so that risk of over-treatment is minimized. For many pts, the value of CTX is documented by the size and molecular marker status of the primary invasive tumor. In others, the value of CTX will be confirmed by histopathologic evidence of metastatic disease in the axillary nodal basin, established by either percutaneous needle biopsy or sentinel lymph node (SLN) biopsy.

Once the decision has been made to pursue neoCTX, the multidisciplinary treatment team should be proactive in designing the management algorithm for the axilla, and this plan should address the pre- as well as post-neoCTX phases. These decisions can have important implications with regard to prognostic value, treatment planning, and surgical morbidity. Reconciling the desires to minimize treatment toxicity while maximizing disease control and information regarding tumor biology can be quite challenging.

The accuracy of SLN biopsy prior to delivery of CTX is well-established. The SLN is clearly more definitive than axillary ultrasound and image-guided FNA biopsy, where the false negative rates approach 20%. Pts that undergo a pre-CTX SLN biopsy documenting node- negative disease are clearly in an advantageous position- these pts can proceed onto neoCTX followed by breast-only surgery/radiation. The major downside to this approach is the need for coordinating the pre-treatment surgical plan.

The algorithm becomes more complex when the neoCTX pt has documented node-positive disease (established via FNA or SLN). For these pts, it is presently unclear whether a completion axillary lymph node dissection (ALND) is always necessary in conjunction with the breast surgery following delivery of the CTX. If clinically-evident axillary disease persists, then ALND will be therapeutic in regional control of disease. If however, the axillary disease appears to have been down-staged, then the value of the completion ALND is less clear. NeoCTX can completely clear nodal metastases in 25% of cases, and in up to half of node-positive breast cancer the initial/pretreatment SLN biopsy will have resected the only metastatic nodes present in the axilla. In this scenario, the completion ALND and documenting the presence versus absence of post-treatment residual disease primarily serves the purpose of providing prognostic value, and potentially affects loco regional radiation planning. Whether or not regional XRT should be routinely offered in lieu of the completion ALND is a subject of ongoing debate.

Another option is to perform post-treatment SLN biopsy for definitive assessment of chemosensitivity in cases of initially node-positive disease, with the hope that a negative post-treatment SLN biopsy can obviate the need for ALND, however single-institution retrospective studies as well as prospective clinical trials (ACOSOG Z1071) have revealed broad variation in accuracy, with SLN false negative rates ranging from 10-40%.

Finally, it has been suggested by many clinicians that neoCTX pts should undergo SLN biopsy following completion of the CTX (concomitantly with their breast surgery) without any up-front axillary staging. This approach avoids multiple exposures to general anesthesia and minimizes likelihood of the pt facing the longterm ALND morbidity. On the other hand, this approach is still fraught with the uncertainty of SLN accuracy related to treatment effects on the false negative rates. Furthermore, this strategy eliminates the possibility of differentiating the pts who presented with node-negative disease from those who were actually node-positive at diagnosis but whose disease was down staged by the neoCTX. It can be argued that this distinction has relevant implications regarding prognosis and benefits of regional XRT.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr CS01-1.