Triple Negative Breast Cancer

Staging & Grading

Staging enables your doctor to develop the best treatment plan for your diagnosis. Along with considering the results of your physical exam, imaging studies and laboratory tests, your doctor will classify and stage the breast cancer according to the tumor, node and metastasis (TNM) system developed by the American Joint Committee on Cancer (AJCC).

In this system, the tumor (T) is categorized according to its size and location; the node (N) category describes whether cancer cells are found in lymph nodes; and the metastasis (M) category indicates whether the cancer has metastasized, or spread, to other parts of the body, such as the bones, brain, liver or lungs (see Table 1). The stage is described by Roman numerals from 0 to IV and the letters A, B or C, if applicable (see Table 2).

Breast cancer is also classified into subtypes based on molecular or genetic changes. Identifying the subtype is important because treatments and 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 to identify the most effective therapy. Tumors can be tested for proteins produced either by the cancer cells themselves or other cells in response to cancer as well as for genetic mutations (see Genetic Testing). 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.

The tables included here share information based on the size and spread of disease. Your final stage will be determined after your doctor considers other factors, such as tumor marker expression and tumor grade. The most well-known tumor markers to guide breast cancer treatment are estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER2) status. As noted above, TNBC is negative for these three markers. The grade is assigned by a pathologist, a doctor who is specially trained to identify diseases by studying cells and tissues under a microscope. Based on the microscopic features of tumor cell growth rate and aggressiveness, the grade helps determine how fast a cancer is likely to grow and spread. Grades range from 1 to 3, and TNBC is often diagnosed as Grade 3, meaning it tends to grow quickly and may spread quickly.

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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