Abstract P3-03-23: Which factor of metastatic lymph nodes–The number, tumor volume or anatomical location–Is independently prognostic in breast cancer? - A prospective cohort study using molecular whole-node analysis of all removed axillary nodes
Authors: Osako T , Iwase T , Ushijima M , Ogiya A , Ueno T , Ohno S , Akiyama F 
Published: May 2019

Abstract
Background: Axillary lymph node status is one of the most powerful prognostic factors in breast cancer. However, it remains unknown which factor of metastatic lymph nodes–the number, tumor volume or anatomical location–is independently prognostic. Conventional pathological examinations of lymph nodes have limited ability to accurately measure metastatic tumor volume due to the partial evaluation of nodes. On the other hand, the one-step nucleic acid amplification (OSNA) assay, a novel molecular method, can quantify the tumor volume in a whole node based on cytokeratin 19 (CK19) mRNA copy number. In this prospective cohort studyusing the OSNA whole-node analysis, we aimed to elucidate the independent prognostic factor of lymph node metastasis in breast cancer.
Patients and Methods: The subjects consisted of 307 cN0 patients with invasive breast cancer, who underwent axillary dissection after a metastatic sentinel node (SN) biopsy and whose SNs and non-SNs were all examined using the OSNA whole-node assaybetween 2009 and 2012.The cut-off values of the OSNA assay for negative/positive results and micro/macrometastasis were defined at 250 and 5,000 copies/μL of CK19 mRNA, respectively. The total tumor volume in the SN or non-SN was defined as the sum of CK19 mRNA copy numbers from all samples in the SN or non-SN. The cut-off value for the total tumor volume in the SN was set at 2,810 copies/μL according to our previous study (Osako et al. Br J Cancer 2017). The anatomical location of metastasis was classified into Level I (confined to SN), Level I (spread to non-SN), or Level II/III. Predictive factors for distant disease-free survival (DDFS) were investigated using the univariate log-rank tests and multivariate Cox proportional hazards models.The median follow-up time was 6.1 years (range, 0.2–8.6).
Results: Of the 307 patients, 130 (42.3%) and 177 (57.7%) had the total tumor volume &lt;2,810 and ≥2,810 copies/μL in the SN, respectively. Five-year DDFS was 96.0% in the entire cohort. In the univariate analysis, DDFS was significantly related to the pT classification, grade, hormone receptor status, triple-negative subtype, total tumor volume in the SN and cytotoxic chemotherapy. However, DDFS was not significantly related to the number of metastatic or macrometastatic nodes in the SN, non-SN, or all nodes (i.e. SN + non-SN); the total tumor volume in the non-SN or all nodes; the AJCC pN classification; or the anatomical location of metastasis. In the multivariate analysis, the total tumor volume in the SN (&lt;2810 vs. ≥2810 copies/μL, hazard ratio 5.2, 95% confidence interval 1.2–23.2, P=0.03) and cytotoxic chemotherapy (- vs. +, hazard ratio 0.05, 95% confidence interval 0.02–0.17, P&lt;0.001) remained significant.
Conclusions: The total tumor volume in the SN was the independent prognostic factor of lymph node metastasis in SN-positive invasive breast cancer. Accurate evaluation of metastatic tumor burden in the SN can be important for predicting prognosis and may help to guide the precise therapeutic decision making for breast cancer patients.
Citation Format: Osako T, Iwase T, Ushijima M, Ogiya A, Ueno T, Ohno S, Akiyama F. Which factor of metastatic lymph nodes–The number, tumor volume or anatomical location–Is independently prognostic in breast cancer? - A prospective cohort study using molecular whole-node analysis of all removed axillary nodes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-23.