Population-based validation of the National Cancer Comprehensive Network recommendations for breast cancer staging

The aim of the current study is to evaluate the performance characteristics of the National Comprehensive Cancer Network (NCCN) staging recommendations for breast cancer with regard to the detection of lung, bone, and liver metastases.

Surveillance, epidemiology, and end points (SEER) database (2010-2015) was accessed, and patients with breast cancer and complete information about T stage and clinical N stage, ER status, Her2 status, and metastatic sites were extracted. Performance characteristics evaluated for the current study included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), number needed to investigate (NNI), and accuracy.

A total of 239,196 patients were included in the analysis. For the overall cohort, the required PPV (for the recognition of lung metastases) is 10.6% and NNI to detect one case of lung metastasis is 9.4. Likewise, PPV (for the recognition of bone metastases) is 18.6% and NNI to detect one case of bone metastasis is 5.3. Moreover, PPV (for the recognition of liver metastases) is 7.6% and NNI to detect one case of liver metastasis is 13.1. When changing the threshold for baseline imaging to includeT2N1 patients, a better balance between sensitivity and specificity among ER+/Her2- patients (> 92% for both sensitivity and specificity for the three metastatic sites) was observed. On the other hand, the proposed change improved sensitivity while it lowers significantly the specificity among Her2+ and triple negative subtypes (specificity < 84% for Her2+ disease for the three metastatic sites; specificity < 87% for triple negative disease for the three metastatic sites).

The current NCCN recommendations for breast cancer staging have an excellent NPV and miss only few patients with lung, liver, or bone metastases. Future studies incorporating the subtype of breast cancer as a determinant of staging pathway is needed.