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The American Society of Breast Surgeons.
Annals of Surgical Oncology

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Prognostic Significance of Residual Axillary Nodal Micrometastases and Isolated Tumor Cells After Neoadjuvant Chemotherapy for Breast Cancer

Stephanie M. Wong MD, MPH, Nora Almana MD, Jungeun Choi MD, Jiani Hu MPH, Haley Gagnon MD, Kelsey Natsuhara MD, Abra H. Shen SB, Stephen DeSantis BSc, Laura Dominici MD, Mehra Golshan MD, Anna Weiss MD, Jennifer Bellon MD, Elizabeth A. Mittendorf MD, PhD, Tari A. King MD
Breast Oncology
Volume 26, Issue 11 / October , 2019



The prognostic significance of low-volume residual nodal disease following neoadjuvant chemotherapy (NAC) is unknown.


Women with cT1–4N0–1 breast cancer treated with NAC were identified from Dana-Farber/Brigham and Women’s Cancer Center (DFBWCC) and the National Cancer Database (NCDB). Disease-free survival (DFS) and overall survival (OS) estimates according to pathologic nodal status were calculated using the Kaplan–Meier method, with Cox proportional hazards regression used to assess the effect of clinical variables on survival outcomes.


Among 967 DFBWCC patients, 27 (2.8%) had residual isolated tumor cells (ITCs) and 61 (6.3%) had micrometastases. Five-year DFS was significantly worse in those with residual ITCs (73.5%) and micrometastases (74.7%) relative to those who were ypN0 following NAC (88.4%, p < 0.001). On adjusted analysis, those with residual ITCs (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.20–3.81) and micrometastases (HR 2.14, 95% CI 1.20–3.81) had increased risk of recurrence relative to ypN0 patients. Among 35,536 NCDB patients, 543 (1.5%) had ITCs and 1132 (3.2%) had micrometastases. Five-year OS estimates were significantly worse with increasing residual nodal burden: ypN0, 88.9%; ypN0[i+], 82.8%; ypN1mi, 79.5%; ypN1, 77.6% (p < 0.001). Compared with patients with ypN0 disease, NCDB patients with ITCs and micrometastases had 1.9- and 2.2-fold risk of death (p < 0.001). On subgroup analysis, the effect of low-volume residual disease on mortality was most pronounced in patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive disease.


Low-volume residual nodal disease following NAC is associated with poorer DFS and OS relative to those who are node negative.

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