Breast Cancer Staging: What the Surgeon and Oncologist Want To Know

Background

The staging of breast cancer has been developed and is maintained by the American Joint Committee on Cancer (AJCC) since 1977. Initially, the goal of breast cancer staging was to identify those patients who would not benefit from radical mastectomy due to their already advanced disease. Traditionally, patients were grouped according to the anatomic extent of their disease based on the TNM system: tumor size, lymph nodes involved, and distant metastasis.

Since the initial implementation of breast cancer staging, it has been found that the anatomic extent of disease is not the only factor that determines outcomes. For example, a large low-grade tumor may have a better outcome compared with a small high-grade tumor. Molecular staging was first introduced in the sixth edition of AJCC but was not fully implemented in clinical breast cancer practice due to lack of prospective data and lack of worldwide availability. Currently, AJCC committee has not switched completely to molecular staging in the current eighth edition because molecular tests are still not available worldwide. Staging is used to guide breast cancer treatment and provide a prognosis to patients. In addition, staging has facilitated less aggressive surgeries, reduced axillary dissection, and decreased mortality by identifying those patients who may benefit from neoadjuvant therapy ( Box 15.1 ).

Eighth Edition of AJCC Cancer Staging Manual

The AJCC staging system provides a strategy for grouping patients for prognosis. The eighth edition of AJCC was implemented on January 1, 2018. The main changes from the prior editions include the implementation of a prognostic staging protocol. In prognostic staging, biological factors such as tumor nuclear grade, hormone receptor status (estrogen receptor [ER]/progesterone receptor [PR]), and human epidermal growth factor 2 (HER2) status are incorporated into the traditional anatomic TNM staging. Commercially available multigene panels (e.g., Oncotype DX, MammaPrint, PAM 50) are also incorporated in limited subgroups. Risk profiles calculated from these biological factors can estimate the 5-year overall survival and disease-specific survival for each anatomic stage of the disease.

Principles and Rules of Staging

At the time of diagnosis, the stage of cancer is a critical factor that defines prognosis and determines the appropriate treatment. Accurate staging is necessary to facilitate the exchange of information among treatment centers and serve as a basis for clinical cancer research. Fig. 15.1 illustrates the AJCC TNM system, which classifies cancers by the size and extent of the primary tumor (T), involvement of lymph nodes (N), and presence or absence of distant metastases (M).

Tumor classification based on the molecular profile is summarized in Table 15.1 . The profiles include Luminal A (71% of tumors, ER or PR is highly positive, the tumor is less aggressive), Luminal B (12% of tumors, ER or PR is low positive, more aggressive than Luminal A), HER2 enriched (5% of tumors, most aggressive tumor), and basal-like. ER and PR are nuclear hormone receptors that modulate the activity of certain genes that control breast cell proliferation; staining of 1% of cells or more is considered positive. HER2 is a member of epidermal growth factor receptors. HER2 is first evaluated by immunohistochemistry: score 0 and 1+ equals HER2 negative, score 2+ equals needs fluorescent in situ hybridization assays (FISH), and score 3+ equals HER2 positive. Additional tumor markers include Ki67, a proliferation marker (graded as <10%, 10%–20%, >20% positivity). Finally, the tumor grade is determined by microscopic evaluation of tubule formation, mitotic count, and nuclear pleomorphism. The tumor grade is classified as low, intermediate, or high grade with an increasing number of scores.

Clinical Versus Pathologic Staging( Table 15.2 )