Abstract

BackgroundLymph node negative (N0) breast cancer can be found coexisting with distant metastasis (DM), which might consequently make clinicians underestimate the risk of relapse and insufficient treatment for this subpopulation.MethodsThe clinicopathological characteristics of N0 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015 were retrospectively reviewed. Multivariate logistic and Cox analyses were used to identify independent risk factors in promoting DM and the 1-, 3-, and 5- year cancer-specific survival (CSS) in this subpopulation.ResultSeven factors including age (<40 years), tumor size (>10 mm), race (Black), location (central), grade (poor differentiation), histology (invasive lobular carcinoma), and subtype (luminal B and Her-2 enriched) were associated with DM, and the area under curve (AUC) was 0.776 (95% CI: 0.763–0.790). Moreover, T1-3N0M1 patients with age >60 years at diagnosis, Black race, triple-negative breast cancer subtype, no surgery performed, and multiple DMs presented a worse 1-, 3-, and 5-year CSS. The areas under the ROC for 1-, 3-, and 5- year CSS in the training cohort were 0.772, 0.741, and 0.762, respectively, and 0.725, 0.695, and 0.699 in the validation cohort.ConclusionThe clinicopathological characteristics associated with the risk of DM and the prognosis of female breast cancer patients without lymph node metastasis but with DM are determined. A novel nomogram for predicting 1-, 3-, 5- year CSS in T1-3N0M1 patients is also well established and validated, which could help clinicians better stratify patients who are at a high-risk level for receiving relatively aggressive management.

Highlights

  • Breast cancer is currently the most frequent malignancy and one of the leading causes of cancer death in the United States [1] and China mainland [2]

  • With the wide application of circulating tumor cell (CTC) analysis, many scholars recognized that the distant metastasis (DM) was considered triggered by hematogenous spread of circulating tumor cells (CTCs), rather than by lymphatic or direct intracavitary spread, which possibly occurred by a different mechanism

  • Despite that we have discovered seven independent risk factors associated with DM in lymph node negative (N0) patients, further studies are needed to verify the underlying molecular mechanisms in promoting this complex process

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Summary

Introduction

Breast cancer is currently the most frequent malignancy and one of the leading causes of cancer death in the United States (estimated 279,100 new cases and 42,690 death) [1] and China mainland (estimated 304,000 new cases and 70,000 deaths) [2]. After surgery, patients with negative lymph node status could remain a favorable outcome, and only a small fraction of them need adjuvant therapy during the postoperative follow-up [11]. Reviewing the recent literature, negative lymph node status was frequently referred to as the “control group” in the study when scholars aimed to explore the risk factors of DM [13,14,15,16]. The insufficient adjuvant therapy and management for this population might increase the risk of relapse in those lymph-nodenegative (N0) patients with multiple risk factors. Clinicians may underestimate the risk of relapse and make insufficient treatment for N0 patients with breast cancer. Lymph node negative (N0) breast cancer can be found coexisting with distant metastasis (DM), which might make clinicians underestimate the risk of relapse and insufficient treatment for this subpopulation

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