Integration the biologic factors into the staging of breast cancer patients with ipsilateral supraclavicular lymph node metastasis

Purpose: To investigate the accuracy and the discriminatory performance in the prognostic prediction in breast cancer (BC) patients with ipsilateral supraclavicular lymph node (ISLN) metastasis using the between the American Joint Committee on Cancer (AJCC) 7th and 8th edition staging system. Methods: Female patients diagnosed as BC were retrieved from the Surveillance, Epidemiology, and End Results database between 2010 and 2014. Chi-squared test, Kaplan-Meier method, Cox proportional hazard analysis, and the receiver operating characteristics were used to conduct statistical analysis. Results: We included 1097 BC patients with ISLN metastasis (N3c disease), including 29.4% (n=322) and 70.6% (n=775) of patients with non-metastatic and metastatic stage at diagnosis, respectively. In non-metastatic stage patients, 64.9% of the patients categorized as having stage IIIC disease in the 7th edition AJCC staging system were downstaged to stage IIIA or IIIB according to the 8th AJCC staging criteria. The AJCC 8th edition staging system had better discriminatory prognostic value than the 7th AJCC staging (area under the curve: 0.586 vs. 0.577, P=0.0006), with a 5-year breast cancer-specific survival (BCSS) rate of 71.3%, 62.2%, 45.2% and 39.1% in stage IIIA, IIIB, IIIC, and IV cohorts, respectively (P<0.0001). The multivariate prognostic analysis revealed that the AJCC 8th edition staging system was an independent prognostic factor for BCSS, while no statistical difference in BCSS was found between the 8th AJCC stage IIIC and IV patients (P=0.188). Conclusion: The AJCC 8th edition pathological prognostic staging showed a better discriminatory prognostic value in ISLN-metastasized breast cancer patients. An additional clarification strategy in stage IIIC disease based on the 8th AJCC staging should be developed to differentiate patients who are curable with multimodality therapy and patients who have less benefit from curative treatment.