New and Important Changes in the TNM Staging System for Breast Cancer

Staging classifications were developed to better understand the clinical behavior of specific malignancies, determine prognosis, and enable physicians and their patients to compare outcomes of similar groups of patients. In the early part of the 20th century, multiple staging classifications were developed by experienced clinicians as well as professional organizations. Starting in 1943, and for the next 10 years, Pierre Denoix, a French surgeon, devised a staging system based on the dimensions of the primary tumor, the presence and extent of regional lymph node metastases, and the presence and absence of distant metastases.1 The system was adopted by the Union Internationale Contre le Cancer (UICC) in 1968, and in 1977, the AJCC published its first staging system based on the TNM concept.2 Since 1977, the AJCC has developed a detailed and extensive staging system that covers the spectrum of human malignancies and has updated it seven times, as new information about clinical behavior and management strategies has become available. Such updates have been the result of multidisciplinary deliberations by teams of experts, including surgeons, medical and radiation oncologists, pathologists, radiologists, and tumor registry experts, including representatives of the AJCC and UICC. In 1987, with the publication of the fourth edition of the UICC TNM Atlas, the UICC and AJCC TNM classifications were unified. The eighth edition of this staging system, which became effective January 1, 2018, is the most dramatic departure from previous staging classification.3 In several tumor types, the new staging system has incorporated biomarkers that modify the anatomic TNM classification. Although such changes were incorporated into staging of a few cancers, including prostate, in the past couple of editions, the paucity of appropriately performed analyses of large clinical databases and relevantly formatted results in the peer-reviewed literature precluded the incorporation of most biomarkers into the staging system. In the meantime, the practice of oncology has moved forward, many biomarkers have been incorporated into the process of selecting therapies, especially systemic therapies, and many cancers have been subdivided into specific subtypes based on these biomarkers. Specifically in the case of breast cancer, it is now considered to be a conglomerate of at least four specific molecular subtypes based on gene expression profiling: luminal A, luminal B, HER2-enriched, and basal breast cancer.4 Because gene expression profiling is not available to most practicing