Triple Negative Breast Cancer

Staging & Grading

Staging the disease is the next step to help your managing physician plan the best treatment for your unique diagnosis. The staging system used for breast cancer was developed by the American Joint Committee on Cancer (AJCC). Known as TNM staging, this system uses the tumor (T), node (N) and metastasis (M) classification (see Table 1).

Results from a physical exam, X-rays and other imaging studies, and laboratory tests offer insight into the tumor’s characteristics, which your managing physician uses for clinical staging.

The T classification is the same for both clinical and pathologic staging and provides information on the size and extent of the tumor within the breast. Clinical staging for the N category describes which lymph nodes have evidence of breast cancer cells. Where the involved lymph nodes are located in the body is important because it shows the extent the disease has spread. The pathologic N category (sometimes denoted as pN) shows how many lymph nodes are involved and the amount of tumor cells actually found in the nodes. The M category indicates whether there is evidence that the cancer has spread to another part of the body beyond the breast and local lymph nodes. Staging for the M category is primarily clinical, although a new M subcategory takes into account the presence of tumor cells that can be detected only by microscopic examination or with molecular testing. The most common sites of distant metastasis in breast cancer are the bones, lungs, liver and brain.

A pathologist examines tissue specimens removed during surgery or biopsy as part of pathologic staging. In addition, the AJCC recommends tissue testing to better determine the treatments that are likely to be most effective. Breast cancer tumors are tested for estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2/neu).

After the breast cancer has been classified, an overall stage is assigned (see Table 2). A grade, which is based on the microscopic features of tumor cell growth rate and aggressiveness, is assigned by a pathologist. Knowing the grade helps determine how fast a cancer is likely to grow and how likely it is to spread. Triple negative breast cancers are often diagnosed as Grade 3, meaning they tend to grow quickly and spread. Higher grade cancers may be more aggressive, but they are still treatable.

Table 1. TNM System for Classifying Breast Cancers

Category 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 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) 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 lymph nodes;
or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes;
or in ipsilateral 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) 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 (on the same side) 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 non-regional nodes, metastases greater than 0.2 mm.

Table 2. Stages of Breast Cancer

Stage TNM Classification
0 Tis, N0, M0
IA T1, N0, M0
IB T0 or T1, N1mi, M0
IIA T0 or T1, N1, M0
T2, N0, M0
IIB T2, N1, M0
T3, N0, M0
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.

 

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