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. 2016 Sep 15;11(9):e0162616.
doi: 10.1371/journal.pone.0162616. eCollection 2016.

Predictive Factors and Value of ypN+ After Neoadjuvant Chemotherapy in Clinically Lymph Node-Negative Breast Cancer

Free PMC article

Predictive Factors and Value of ypN+ After Neoadjuvant Chemotherapy in Clinically Lymph Node-Negative Breast Cancer

Ippei Fukada et al. PLoS One. .
Free PMC article


Background: Pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) has been regarded as a surrogate endpoint for disease-free survival (DFS) and overall survival (OS) of patients with breast cancer. No consensus regarding the definition of pCR has been established; there are several definitions according to a variety of classifications. Eradication of cancer cells in both breast and lymph nodes has been better associated with improved prognosis than in the breast alone. Even in patients diagnosed as having clinically node-negative cancer before NAC, postoperative pathological examination often shows axillary lymph node metastases.

Patients and methods: Of the 771 patients with breast cancer who underwent NAC in the Cancer Institute Hospital between January 2000 and May 2009, 146 patients preoperatively diagnosed as having node-negative breast cancer were retrospectively evaluated. We have made the definition of clinically lymph node-negative (N0) as follows: first, ultrasonography before NAC did not show any lymphadenopathy. Second, a cytological procedure confirmed negative study for each patient when ultrasonography suggested lymphadenopathy.

Results: The median observation period was 79.7 months, and the median age of the subjects was 51 years. Pathological examination at the time of the surgery showed lymph node metastases (ypN+) in 46 patients (31.5%). Histological therapeutic effects revealed ypT0/is in 9 patients (6.2%) and ypTinv in 137 (93.8%). Multivariate analysis demonstrated that younger age (49>), large tumor size, NG3, and ypN+ were significant poor prognostic factors for DFS (p = 0.020, p = 0.008, P = 0.022 and p = 0.010, respectively). Moreover, ypN+ was the only significant poor prognostic factor for OS (p = 0.022). The predictive factors of ypN+ in clinically lymph node-negative breast cancer were ypTinv (p = 0.036) and the luminal type (HR+ and HER2-) (p = 0.029).

Conclusion: The prognosis of clinically lymph node negative breast cancer depended on ypN+, which was associated with ypTinv and luminal subtype.

Conflict of interest statement

The authors have declared that no competing interests exist.


Fig 1
Fig 1. Study profile.
Fig 2
Fig 2. The Kaplan-Meier plots of DFS and OS.
(A) The median DFS was significantly longer in patients with ypN0 than ypN+ (105.9 vs 97.0 months, p = 0.007). (B) There was also significant difference in the median OS (110.8 vs 107.4 months, p = 0.007). Abbreviations: ypN0: No invasive residual in nodes, ypN+: invasive or noninvasive residuals in the breast, infiltrated lymph nodes.

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Grant support

The authors received no specific funding for this work.