Breast Cancer

Staging

People who have breast cancer are frequently asked about the stage of their disease. Generally, a lower stage, such as Stage I, is often curable, whereas a higher stage cancer, such as Stage IV, indicates a more serious prognosis. Your doctor uses the staging process to determine the extent of your cancer, where it is located and whether it has metastasized (spread) to nearby organs, tissues or lymph nodes, or to other parts of your body. That information helps your doctor determine the treatment approach that is likely to be most effective for you.

The results of a biopsy, imaging scans, immunohistochemistry and genomic testing are used to classify and stage all types of breast cancer according to the American Joint Committee on Cancer (AJCC). The system includes the tumor (T) size, cancer cells found in nearby lymph nodes (N), and cancer that has metastasized (M), or spread, to other parts of the body (see Table 1).

The T classification categories are the same for both clinical and pathologic staging and provide information on the size and extent of the tumor within the breast. Clinical T (described as cT) refers to the tumor size estimate based on physical/clinical examination and breast imaging; pathologic T (described as pT) refers to the size of the tumor when it has been removed and measured in the pathology laboratory.

Clinical classification for the N category (cN) describes the location and bulkiness of lymph nodes (usually in the axilla, under the arm) that appear to be malignant (from spread of the breast cancer) upon physical examination. Location and extent of any cancerous lymph nodes provide clues regarding the likelihood that the breast cancer might have spread to other organs.

The pathologic N category (pN) is determined postoperatively and describes how many lymph nodes are involved.

The M category indicates whether the cancer has metastasized to another part of the body beyond the breast and nearby lymph nodes.

After breast cancer is classified, it is staged (see Table 2).

Stage 0 refers to ductal carcinoma in situ (DCIS) breast cancer, and Stage IV represents breast cancer that has spread beyond the breast and lymph nodes into distant organs, such as the bones, brain, liver or lungs. Regardless of where the cancer spreads, it is still considered breast cancer and is treated as such.

This information and many other important factors are considered and documented on your pathology report before you receive your final stage.

A pathology report (sometimes called a surgical pathology report) is a medical report that describes the characteristics of a tissue specimen that is taken from a patient. The pathology report is written by a pathologist, a doctor who has special training in identifying diseases by studying cells and tissues under a microscope. The pathology report provides the definitive cancer diagnosis. Tumor grade, biomarkers, and molecular and genetic changes in cancer tissue identified in multigene panels are also considered and included on the pathology report and may be considered for staging.

Immunohistochemistry, a type of test used to help diagnose cancer, may be performed on the initial biopsy material and will include the tumor’s estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status to determine the presence (ER+/PR+/HER2+) or absence (ER-/PR-/HER2-) of these hormone receptors.

The hormone-related biomarkers ER and PR send signals to special receptor proteins inside normal breast cells and some breast cancer cells (those that carry the ER and/or PR biomarkers) to “turn on” the growth of cells.

Approximately 20 percent of all breast cancers make extra copies of HER2, which 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 of the hormone receptors or the HER2 receptor is referred to as triple negative breast cancer (TNBC), which is an aggressive form of breast cancer.

Determining whether you have hereditary breast cancer is also important. The BReast CAncer 1 (BRCA1) and BReast CAncer 2 (BRCA2) genes are the most common hereditary susceptibility genes, and your doctor may test for others. Individuals who have inherited abnormalities in the BRCA1 or BRCA2 genes have an increased likelihood of developing breast cancer and/or ovarian cancer.

Newly-diagnosed breast cancer patients found to have a BRCA mutation face an increased risk of another new breast cancer. As a result, the presence of inherited mutations in the BRCA1 and BRCA2 genes or other cancer-susceptibility genes may influence decisions regarding cancer prevention (prophylactic) surgery (removal of the breasts and/or ovaries). The discovery of these mutations may also lead to different systemic treatments.

If breast cancer recurs, your doctor will perform diagnostic tests to determine whether the stage and classification have changed, which in turn may lead to different treatment recommendations.

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 Tumor ≤ (not more than) 20 mm in greatest dimension.
T1mi Tumor ≤ (not more than) 1 mm in greatest dimension.
T1a Tumor > (more than) 1 mm but ≤ (not more than) 5 mm in greatest dimension.
T1b Tumor > (more than) 5 mm but ≤ (not more than) 10 mm in greatest dimension.
T1c 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 Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules).
T4a Extension to the chest wall.
T4b 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.
T4c Both T4a and T4b are present.
T4d Inflammatory carcinoma.
Node (N)
pNX Regional lymph nodes cannot be assessed.
pN0 No regional lymph node metastasis identified or ITCs (isolated tumor cells) only.
pN0(i+) ITCs (isolated tumor cells) only (malignant cell clusters no larger than 0.2 mm) in regional lymph node(s).
pN0(mol+) Positive molecular findings by reverse transcriptase polymerase chain reaction (RT-PCR); no ITCs (isolated tumor cells) detected.
pN1 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.
pN1mi Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm).
pN1a Metastases in 1-3 axillary (armpit) lymph nodes, at least one metastasis larger than 2.0 mm.
pN1b Metastases in ipsilateral (on the same side) internal mammary sentinel nodes, excluding ITCs (isolated tumor cells).
pN1c pN1a and pN1b combined.
pN2 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.
pN2a Metastases in 4-9 axillary (armpit) lymph nodes (at least one tumor deposit larger than 2.0 mm).
pN2b Metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary (armpit) nodes.
pN3 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.
pN3a 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.
pN3b pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging);
or pN2a in the presence of pN1b.
pN3c 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.