br Methods br Study design
This study was approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board. From our multidisciplinary breast cancer database of consecutive 13,042 patients who received definitive surgery for non-metastatic, invasive breast cancer between 1998 and 2013, women who had a regional NR as the first relapse and dedicated imaging (magnetic resonance imaging or computed tomography [CT] with or without positron emission tomography of the NR were identified. For pa-tients who received radiation, 3D-conformal methods were used throughout the study period, and all nodal regions were contoured and assessed by dose-volume histogram when evaluating the treatment plan. Patients with initial stage IV breast cancer, history of noncutaneous malig-nancies (except melanoma), incomplete medical records, contralateral NR or chest wall or breast-only recurrence (without a component of NR) and evidence of distant me-tastases >1 month from the diagnosis of NR were excluded. In patients lacking a corresponding biopsy of the NR, radiographic features of malignancy such as those nodes >1 cm in short axis, extent of fluorodeoxyglucose-avidity (if positron emission tomography was used), infil-trative borders, and inhomogeneous enhancement were used as criteria to determine an NR.
Mapping of NR
All cases of NR were mapped manually using CT imaging of a female patient who had undergone left-sided mastec-tomy and sentinel node biopsy without reconstruction. Her CT scan of the chest with intravenous Lovastatin acquired with both arms abducted overhead and uploaded onto the Pinnacle planning system (Philips Health Care).
The spatial locations of the NRs were transferred to the template CT. The epicenter of each NR was identified as the center of a 5-mm circle. Transferred recurrences were cen-trally reviewed by the study radiation oncologists (C.D. and A.H.) and radiologist (J.T.). A red circle represented NR cases in patients who received RT as part of primary treat-ment, and a yellow circle represented those who did not.
Volume 103 Number 3 2019 Nodal recurrences in breast cancer 585 Statistics Patterns of nodal recurrences
The c2 or Fisher exact test was used to compare patterns of NR. Multivariate Cox proportional hazard regression models were used to correlate clinical and pathologic features to NR. Kaplan-Meier plots were performed for each patient cohort, and 2-year landmark analysis from time of surgery for the primary breast cancer was used to plot survival.
Patient and disease characteristics
The study population included 153 patients with 243 NRs, whose key clinical characteristics at the time of diagnosis for their primary breast cancer are described in Table 1. Relative to the index population of 13,042 women with nonmetastatic breast cancer, the NR study population was younger (median age, 51 years; range, 23-79 years), and the majority had grade 3 disease (68% vs 25%; P Z .02). More than half (51.3%) of the NR population had lymphovas-cular invasion (LVI; 51% vs 31%; P Z .02). NR patients were less frequently ER positive (46% vs 75%; P Z .02). Extracapsular extension (ECE) was more common in the NR group (22% vs 14%; P Z .03). The majority (52%) of the NR study population presented with 0 positive lymph nodes, followed by 31.2% receiving 1 to 3 nodes and 17% receiving 4 positive nodes. Overall, 60% and 84% of the study population received some form of adjuvant RT or chemotherapy, or both.
NRs were confirmed by pathology in 73% (112/153) of patients and clinical and radiographic findings for the remaining 26% (40/153) of patients; 44% of patients had isolated NR, and 56% of patients had sites of distant metastasis that were identified at the time of (but not before) the NRs. Lastly, 19% had a synchronous breast or chest wall failure and NR.
Given the high rate of out-of-field recurrences in the SCV, we formulated definitions for the medial, lateral, and