How Often Does Retrieval of a Clipped Lymph Node Change Adjuvant Therapy Recommendations? A Prospective, Consecutive, Patient Cohort Study.

BACKGROUND: Prior studies examining sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for cN1 patients have demonstrated that 20% of biopsied, clipped lymph nodes (cLNs) are nonsentinel lymph nodes (non-SLNs). Our goal was to determine how often the cLN was a non-SLN among both cN0 and cN1 patients and how often cLN pathology impacted management. METHODS: Overall, 238 patients treated with NAC and surgery January 2019 to June 2020 were prospectively examined. Patients underwent routine axillary ultrasound, biopsy of suspicious nodes, and clip placement. Radioactive iodine-125 seed localization of the cLN was performed in cN1 patients only. Isolated tumor cells (ITCs) were considered node positive (ypN+) for both cN0 and cN1 cohorts. Chart review was performed to determine if cLNs were non-SLN and their ypN status. RESULTS: Of 118 cN0 patients, 115 of 118 (97%) underwent successful SLNB, 33 of whom had a cLN present; 21 of 33 (64%) cLNs were non-SLNs. Overall, 9 of 118 (8%) were ypN+; no cLN was ypN+ without additional +SLNs. Of 120 cN1 patients, 104 of 120 (87%) converted to cN0, 98 of 104 (94%) of which had attempted SLNB, and 95 of 98 (97%) successfully mapped. The cLN was a non-SLN in 18 of 95 (19%). Overall, 58 of 104 (56%) cN1 patients were ypN+. One patient had a positive cLN in the absence of +SLNs. This patient underwent axillary lymph node dissection (ALND); adjuvant treatment recommendations were unchanged. CONCLUSIONS: The cLN was a non-SLN in 19% of cN1 patients. cLN pathology did not impact adjuvant therapy recommendations, calling into question the utility of routinely clipping biopsied lymph nodes.

Oncotype DX testing in node-positive breast cancer strongly impacts chemotherapy use at a comprehensive cancer center.

PURPOSE: In 2016, we initiated standardized "reflex" Oncotype DX Recurrence Score (RS) testing for patients ≤ 65 years with pT1-2N0-1 HR+/HER2- breast cancer. Here, we examine RS testing patterns, RS distribution, and factors associated with chemotherapy use in patients with pN1 breast cancer. METHODS: Patients with stage I-III HR+/HER2- pN1 breast cancer treated with upfront surgery from February 2016 to March 2019 were identified. Clinical characteristics were compared between patients meeting reflex RS testing criteria, those with RS ordered outside of reflex criteria, and those without RS testing. RS was categorized as low (< 18), intermediate (18-30), and high (≥ 31). Multivariate logistic regression was performed to identify factors associated with adjuvant chemotherapy receipt. We examined 3-year recurrence-free survival (RFS) and overall survival (OS) stratified by chemotherapy use. RESULTS: We identified 347 HR+/HER2- pN1 patients; 272 (78.4%) received RS testing, and 194 (71.3%) met reflex criteria. RS was < 18 in 164 (61.4%) patients, 18-30 in 89 (32.7%) patients, and ≥ 31 in 16 (5.9%) patients. On multivariate analysis, RS < 18 (OR 0.47, 95% CI 0.24-0.92) was associated with lower odds of chemotherapy use, whereas presence of lymphovascular invasion (OR 1.77, 95% CI 1.03-3.07) and lobular subtype (OR 2.40, 95% CI 1.21-4.78) were associated with higher odds. No differences in 3-year RFS (p = 0.97) or OS (p = 0.19) based on chemotherapy receipt were observed. CONCLUSION: Most RS-tested HR+/HER2- pN1 patients at our center had low genomic risk. A low RS independently influenced chemotherapy omission and in RS-tested patients, short-term outcomes were excellent. Our study demonstrates increased use of RS in guiding adjuvant treatment decisions in node-positive disease.

Investigation of parameters that determine Nano-DC vaccine transport.

Effective migration of dendritic cells into the lymphatic system organs is the prerequisite for a functional dendritic cell vaccine. We have previously developed a porous silicon microparticle (PSM)-based therapeutic dendritic cell vaccine (Nano-DC vaccine) where PSM serves both as the vehicle for antigen peptides and an adjuvant. Here, we analyzed parameters that determined dendritic cell uptake of PSM particles and Nano-DC vaccine accumulation in lymphatic tissues in a murine model of HER2-positive breast cancer. Our study revealed a positive correlation between sphericity of the PSM particles and their cellular uptake by circulating dendritic cells. In addition, the intravenously administered vaccines accumulated more in the spleens and inguinal lymph nodes, while the intradermally inoculated vaccines got enriched in the popliteal lymph nodes. Furthermore, mice with large tumors received more vaccines in the lymph nodes than those with small to medium size tumors. Information from this study will provide guidance on design and optimization of future therapeutic cancer vaccines.

Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection.

PURPOSE: Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. METHODS: A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). RESULTS: Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). CONCLUSION: Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.