What is the TNM (Tumor, Node, Metastasis) staging system for breast cancer?

TNM Staging of Breast Cancer

Use the 8th edition AJCC TNM staging system for breast cancer, which integrates anatomic extent of disease (tumor size, nodal involvement, metastases) with prognostic biomarkers including hormone receptor status, HER2 expression, and tumor grade to determine final prognostic stage groups. 1, 2

Core TNM Components

T (Primary Tumor) Classification

• T1: Tumor ≤20 mm in greatest dimension 1
• T2: Tumor >20 mm but ≤50 mm 3
• T3: Tumor >50 mm in greatest dimension 3
• T4a: Extension to chest wall (not including pectoralis muscle adherence alone) 3
• T4b: Ulceration and/or ipsilateral satellite nodules and/or skin edema (not meeting inflammatory carcinoma criteria) 3
• T4c: Both T4a and T4b features present 3
• T4d: Inflammatory carcinoma 3

N (Regional Lymph Nodes) Classification

Critical 8th edition changes distinguish micrometastases from isolated tumor cells based on size and histologic activity: 1

• pN0(i+): All metastatic lesions ≤0.2 mm detected by H&E or IHC 1
• pN0(i-): No detectable tumor cells by H&E or IHC 1
• pN1mi: Micrometastases >0.2 mm but ≤2.0 mm 1
• pN1: 1-3 axillary lymph nodes involved, or internal mammary nodes detected by sentinel node procedure only 1, 3
• pN2a: 4-9 axillary lymph nodes involved 1
• pN2b: Internal mammary nodes detected clinically/by imaging without axillary involvement 1, 3
• pN3: ≥10 axillary nodes, or infraclavicular nodes, or internal mammary nodes with axillary involvement, or supraclavicular nodes 1, 3

Major staging revision: Supraclavicular node metastases are now classified as N3 disease (previously M1), making them potentially curable with aggressive locoregional therapy. 1

M (Distant Metastasis) Classification

• M0: No distant metastases 1
• M1: Distant metastases present 1

Stage Groupings

Early Stage Disease

• Stage I-II: Operable local-regional invasive carcinoma 2
• Stage 0: Pure noninvasive carcinomas (DCIS, LCIS) 2

Locally Advanced Disease

• Stage IIIA: T3N1M0, T0-2N2M0, or T3N2M0 3
• Stage IIIB: T4N0-2M0 (inoperable locally advanced disease) 3
• Stage IIIC: Any T, N3, M0 (created specifically to identify this high-risk subset) 1, 3

Integration of Biomarkers in 8th Edition

The revolutionary change in the 8th edition is incorporation of prognostic biomarkers beyond anatomic staging to yield final prognostic stage groups: 4

Required Biomarker Assessment

• Estrogen receptor (ER) and progesterone receptor (PR) status must be determined for all invasive breast cancers by immunohistochemistry 1, 2
• HER2 status determination is mandatory, with ambiguous IHC results (2+) requiring FISH or CISH confirmation 2
• Tumor grade using standardized grading systems 1
• Multigene panel recurrence scores (when available) can downstage some ER-positive, lymph node-negative tumors 1

Clinical vs. Pathological Staging

Pathological staging (pTNM) is more accurate than clinical staging (cTNM) and should be used when available following surgical resection: 2

• Clinical staging (cTNM): Based on physical examination, imaging, and biopsy before treatment 2
• Pathological staging (pTNM): Based on surgical specimens after surgery, includes total number of removed and positive lymph nodes, extent of nodal metastases, histological type and grade, resection margins, and vascular invasion 1

Required Staging Workup

Routine Evaluation for Early Breast Cancer

• Full blood count, liver and renal function tests, alkaline phosphatase, calcium levels before surgery and systemic therapy 1
• Avoid comprehensive laboratory tests and radiological staging in asymptomatic patients with early disease—distant metastases are rare and most patients do not benefit 1

Extended Staging for High-Risk Features

Obtain CT chest, abdominal imaging (US/CT/MRI), and bone scan for patients with: 1

• Clinically positive axillary nodes
• Large tumors (≥5 cm)
• Aggressive biology
• Clinical signs, symptoms, or laboratory values suggesting metastases

Locally Advanced Disease Workup

Comprehensive staging must include: 3

• History, physical examination, complete blood count, platelet count, liver function tests, alkaline phosphatase 3
• Chest X-ray or CT, abdominal imaging (CT/US/MRI), bone scan, diagnostic bilateral mammogram 3
• Pathology review with ER/PR and HER2 status determination 3
• Genetic counseling if high-risk for hereditary breast cancer 3

Critical Pathology Reporting Requirements

Accurate pathology reporting requires communication between clinician and pathologist about: 1

• Relevant patient history, prior breast biopsies, prior chest irradiation, pregnancy status
• Characteristics of abnormality biopsied (palpable, mammographic, microcalcifications)
• Clinical lymph node status, inflammatory changes, skin abnormalities
• Any prior treatment (chemotherapy, radiation)
• Specimen orientation and specific biomarker requests

Common pitfall: National surveys show up to 50% of breast cancer pathology reports are missing critical elements, particularly surgical margin orientation/reporting and consistent tumor grading. 1

Clinical Application by Stage

Operable Disease (Stage I-II, Some IIIA)

• Breast-conserving surgery with radiation or mastectomy 2
• Systemic therapy decisions based on tumor biology (hormone receptor and HER2 status) 2

Locally Advanced Disease (Stage IIIB-IIIC)

Critical distinction: Operable locally advanced disease (T3N1M0) can achieve pathologically negative margins; inoperable disease requires neoadjuvant chemotherapy before definitive surgery. 3

• Neoadjuvant chemotherapy preferred for stage II-III triple-negative breast cancer 2
• Dose-dense anthracycline and taxane-based regimens preferred for neoadjuvant treatment 2

Evolution and Rationale of TNM System

The TNM system was designed to quantify anatomical burden of cancer and became synonymous with prognosis due to consistent, robust associations between anatomical extent and patient outcomes. 1

• The system's simplicity and ease of use led to worldwide adoption 1
• Anatomical disease stage is more consistent over time and across geographical areas compared to molecular prognostic factors 1
• The UICC and AJCC collaborate to ensure minimal differences between their TNM classifications, striving for congruent definitions since 1987 1