Advanced Breast Cancer

Staging

Determining the stage of your cancer will help your doctor determine your treatment plan. Breast cancer is classified and staged according to the tumor, node and metastasis (TNM) system developed by the American Joint Committee on Cancer (AJCC). Doctors categorize the tumor (T) according to its size and location, whether cancer cells are found in nearby lymph nodes (N) and whether the cancer has metastasized (M) to other parts of the body, such as the bones, brain, liver or lungs (see Tables 1 and 2).

These tables share information based on the size and spread of disease. Your final stage will be determined after your doctor also considers other factors, such as tumor grade and biomarker expression. The grade indicates how fast a cancer is likely to grow and spread. The most well-known biomarkers to guide breast cancer treatment are estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). Results of multi-gene panels, such as MammaPrint, Oncotype DX 21-gene recurrence score, PAM 50 (Prosigna) and the Breast Cancer Index, may be considered to guide treatment planning.

Breast cancer is also classified into subtypes based on molecular or genetic changes. Knowing the subtype is important because monitoring milestones, such as the length of time without progression and response to therapy, will vary by subtype.

As a result, AJCC recommends molecular testing along with staging. Patients with advanced/metastatic breast cancer will generally need to undergo a biopsy of the metastatic site(s) to confirm the diagnosis and also to assess biomarkers on the areas where the breast cancer has spread. Sometimes these biomarkers are different compared to the original biopsy of the tumor in the breast, and your doctor needs this information to plan your treatment.

Table 1. AJCC TNM System for Classifying Breast Cancer

Classification Definition
Tumor (T)
Tx Primary tumor cannot be assessed.
T0 No evidence of primary tumor.
Tis (DCIS) Ductal carcinoma in situ.
Tis (Paget) Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma (tissue).
T1
  T1mi
  T1a
  T1b
  T1c
Tumor ≤ (not more than) 20 mm in greatest dimension.
Tumor ≤ (not more than) 1 mm in greatest dimension.
Tumor > (more than) 1 mm but ≤ (not more than) 5 mm in greatest dimension.
Tumor > (more than) 5 mm but ≤ (not more than) 10 mm in greatest dimension.
Tumor > (more than) 10 mm but ≤ (not more than) 20 mm in greatest dimension.
T2 Tumor > (more than) 20 mm but ≤ (not more than) 50 mm in greatest dimension.
T3 Tumor > (more than) 50 mm in greatest dimension.
T4
 
  T4a
  T4b


  T4c
  T4d
Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules).
Extension to the chest wall.
Ulceration and/or ipsilateral (on the same side) macroscopic satellite nodules and/or edema (including peau d’orange) of the skin that does not meet the criteria for inflammatory carcinoma.
Both T4a and T4b are present.
Inflammatory carcinoma.
Node (N)
pNx Regional lymph nodes cannot be assessed.
pN0  
  pN0(i+)
 
  pN0(mol+)
No regional lymph node metastasis identified or ITCs (isolated tumor cells) only.
ITCs (isolated tumor cells) only (malignant cell clusters no larger than 0.2 mm) in regional lymph node(s).
Positive molecular findings by reverse transcriptase polymerase chain reaction (RT-PCR); no ITCs (isolated tumor cells) detected.
pN1
 

  pN1mi
  
  pN1a
  pN1b
  
  pN1c
Micrometastases; or metastases in 1-3 axillary (armpit) lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy.
Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm).
Metastases in 1-3 axillary (armpit) lymph nodes, at least one metastasis larger than 2.0 mm.
Metastases in ipsilateral (on the same side) internal mammary sentinel nodes, excluding ITCs (isolated tumor cells).
pN1a and pN1b combined.
pN2
  

  pN2a
  
  pN2b
Metastases in 4-9 axillary (armpit) lymph nodes; or positive ipsilateral (on the same side) internal mammary lymph nodes by imaging in the absence of axillary (armpit) lymph node metastases.
Metastases in 4-9 axillary (armpit) lymph nodes (at least one tumor deposit larger than 2.0 mm).
Metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary (armpit) nodes.
pN3
  






  pN3a


  pN3b

  pN3c
Metastases in 10 or more axillary (armpit) lymph nodes;
or in infraclavicular (below the clavicle) (Level III axillary [armpit]) lymph nodes;
or positive ipsilateral (on the same side) internal mammary lymph nodes by imaging in the presence of one or more positive Level I, II axillary (armpit) lymph nodes;
or in more than three axillary (armpit) lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral (on the same side) internal mammary lymph nodes;
or in ipsilateral (on the same side) supraclavicular (above the clavicle) lymph nodes.
Metastases in 10 or more axillary (armpit) lymph nodes (at least one tumor deposit larger than 2.0 mm); or metastases to the infraclavicular (below the clavicle) (Level III axillary [armpit]) lymph nodes.
pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging); or pN2a in the presence of pN1b.
Metastases in ipsilateral supraclavicular (above the clavicle) lymph nodes.
Note: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or FNA/core needle biopsy respectively, with NO further resection of nodes.
Metastasis (M)
M0 No clinical or radiographic evidence of distant metastases.
cM0(i+) No clinical or radiographic evidence of distant metastases in the presence of tumor cells or deposits no larger than 0.2 mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastases.
cM1 Distant metastases detected by clinical and radiographic means.
pM1 Any histologically proven metastases in distant organs; or if in nonregional nodes, metastases greater than 0.2 mm.

Table 2. Stages of Advanced Breast Cancer

Classification Definition
IIIA T0-T3, N2, M0
T3, N1, M0
IIIB T4, N0-N2, M0
IIIC Any T, N3, M0
IV Any T, Any N, M1

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer Science+Business Media.

 

Advanced Breast Cancer Staging Illustrations

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