Breast Cancer

Staging

Your doctor will develop the best treatment plan for your unique diagnosis based on the stage of the disease, along with some alternatives that might best fit your quality of life. The stage is determined from the results of a physical exam, imaging studies and laboratory tests. 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 system (see Table 2). When staging breast cancer in the United States, additional factors are also considered with the TNM. These include tumor grade, HER2/ER/PR status and multi-gene panels, including MammaPrint or Oncotype DX.

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 the location and bulkiness of lymph nodes that seem to be malignant (from spread of the breast cancer) on physical examination. Location and extent of any cancerous lymph nodes provide clues regarding likelihood that the breast cancer might have spread to other organs. The pathologic N category (sometimes denoted as pN) describes how many lymph nodes are involved and the amount of tumor cells actually found in the nodes, based upon needle biopsy and/or surgical resection. 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. The most common sites of distant metastasis in breast cancer are the bones, lungs, liver and brain.

Researchers have found that breast cancer tumors vary in several important ways. The identification of tumor markers, or biomarkers, and the development of technology for genetic profiling (studying several genes in a tumor simultaneously) have led to the classification of breast cancer according to subtypes based on molecular or genetic changes. The distinction among these subtypes is important because treatments and monitoring milestones, such as the length of time without progression and response to therapy, vary by subtype. As a result, the AJCC recommends tissue testing along with staging to identify the most effective therapy. Tumors can be tested for proteins produced either by the cancer cells themselves or by other cells in response to cancer, as well as for genetic mutations linked to the development of cancer.

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). Estrogen and progesterone are hormones that circulate naturally in the body, sending signals to special receptor proteins inside normal breast cells. These hormones can also send signals to some breast cancer cells (those that carry the ER and/or PR biomarkers) to “turn on” the growth of breast cancer cells. Breast cancers are also classified according to the presence (ER+/PR+) or absence (ER-/PR-) of these receptors in the cells, and the amount (or expression) of receptors. Approximately 20 percent of all breast cancers make extra copies of the HER2 gene that encodes a growth-promoting protein. Breast cancers with too much of this protein tend to grow and spread more aggressively. Breast cancer that does not express either the hormone receptors or the HER2 receptor is referred to as “triple negative breast cancer.”

The presence of the BRCA1 and BRCA2 genetic mutations increase the risk for breast cancer. Identification of hereditary breast cancer is now becoming important in treatment decisions. Studies have shown that tumors with BRCA1 and/or BRCA2 mutations have distinct characteristics that may make some types of targeted therapy more effective than traditional treatment strategies (see Tumor Markers). A pathologist will examine tissue specimens removed during surgery or biopsy as part of pathologic staging.

After breast cancer is classified, it is staged (see Table 1). Stage 0 breast cancer is also referred to as in situ breast cancer or noninvasive breast cancer, and Stage IV represents breast cancer that has spread beyond the breast into nearby nodes and tissues. The staging system and prognostic stage accounts for biomarker expression and tumor grade, as well as tumor size and nodal status.

Table 1. 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

Table 2. 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.

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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