Histologic Changes Associated With False-Negative Sentinel Lymph Nodes After Preoperative Chemotherapy in Patients With Confirmed Lymph Node-Positive Breast Cancer Before Treatment

Lymphatic mapping and sentinel lymph node (SLN) biopsy have become routine procedures for patients with early stage breast cancer, as they provide a minimally invasive method of assessing axillary lymph node status.1–5 Patients with negative SLNs have a low likelihood of having metastases in nonsentinel axillary lymph nodes, so such patients can be spared the morbidity of an axillary lymph node dissection. Even in patients who receive preoperative chemotherapy, also known as neoadjuvant or induction chemotherapy, SLN biopsy has been reported to be an accurate method for staging the axilla.6,7 However, there has also been concern that lymphatic fibrosis or tumor debris could alter lymphatic draining patterns and decrease the accuracy of SLN biopsy in these patients. The false-negative rates for SLN biopsy after preoperative chemotherapy have been reported to range from 0% to 33%.6,8–14 Although the number of patients in each series is relatively small, a recent meta-analysis concluded that the SLN biopsy is accurate after neoadjuvant chemotherapy.7 Most investigators have focused on patients who present with clinically lymph node-negative disease before chemotherapy, and have largely excluded patients with confirmed lymph node-positive disease at initial presentation.8–14 At our institution, we have noted a higher false-negative rate for SLN biopsy after chemotherapy in patients with confirmed lymph node-positive disease before treatment.15 We hypothesized that particular histologic features in negative SLNs after preoperative chemotherapy in this patient population might help to predict the likelihood of a false-negative SLN. Histologic findings indicative of treatment effect, such as fibrosis, characteristically occur at the site of a tumor that undergoes a partial or complete pathologic response to chemotherapy.16,17 Positive SLNs that undergo a complete pathologic response to chemotherapy would be expected to have similar histologic findings. In patients with a fine-needle aspiration (FNA)-proven positive lymph node before chemotherapy, the SLN might not be the same as the FNA-proven positive lymph node. However, non-SLNs are expected to be positive only when the SLN is also positive. Therefore, all patients with an FNA-proven positive lymph node are expected to have had positive SLNs. A positive SLN after treatment is expected to have fibrosis or other treatment-related changes. If fibrosis or other changes associated with tumor response are not observed in the SLN after chemotherapy in a patient with confirmed lymph node-positive disease before treatment (ie, in a patient expected to have had a positive sentinel lymph node before treatment), the apparent SLN might not be the true SLN. Treatment-induced lymphatic fibrosis or tumor debris could have altered the normal lymphatic draining pattern. Therefore, the absence of such histologic changes in a negative SLN after chemotherapy in a patient with confirmed lymph node-positive disease before treatment should raise the possibility of a false-negative SLN. The purpose of this study was to determine whether histologic findings in negative SLNs after chemotherapy can predict the accuracy of SLN biopsy in patients who present initially with confirmed lymph node-positive disease.