The results of a biopsy, blood tests, imaging scans, and genomic and genetic testing are used to classify and stage breast cancer according to the tumor, node and metastasis (TNM) system. Developed by 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, such as the bones, brain, liver or lungs (see Table 1).
After it is classified, it is staged (see Table 2). Stage 0 breast cancer refers to in situ breast cancer (DCIS), and Stage IV represents breast cancer that has spread beyond the breast and lymph nodes into distant organs.
The results of a biopsy, imaging scans, immunohistochemistry and genomic testing are used to classify and stage breast cancer, according to the American Joint Committee on Cancer (AJCC). Immunohistochemistry on the initial biopsy material 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+) or absence (ER-/PR-) of these hormone receptors. Before a final stage is determined, tumor grade, biomarkers and molecular and genetic changes in cancer tissue identified in multigene panels are also considered.
Ongoing biomarker tests to monitor the cancer and its treatment or disease progression may produce different results. In that case, the cancer may be restaged and the treatment plan modified accordingly. Changes in test results or symptoms may be a good time to seek a second opinion from an experienced specialist. Another opinion can confirm the treatment plan or offer new options.
The hormones estrogen and progesterone 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. As a result, breast cancers are classified according to the presence (ER+/PR+) or absence (ER-/PR-) of these hormone receptors in the cells, and the amount (or expression) of receptors. 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).
Determining whether you have hereditary breast cancer is important. The breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes are the most commonly tested for, and your doctor may include others. Individuals that 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. The presence of inherited mutations in the BRCA1 and BRCA2 genes or other cancer-susceptibility genes may therefore influence decisions regarding cancer prevention (prophylactic) surgery (removal of the breasts and ovaries). These mutations may also lead to different systemic treatments.
Having an inherited mutation does not mean you will automatically develop cancer; it means the risk is increased and you can explore ways to lower it, such as preventive surgery, medication or lifestyle changes. Frequent screenings will most likely result in early detection. Risk factors for hereditary breast cancer predisposition related to carrying a BRCA mutation include:
- Family history of any cancer, especially rare, ovarian and male breast cancers
- Cancer at an early age
- Personal history of TNBC
- Multiple cancers in one relative
- Ancestry, such as Ashkenazi Jewish heritage
Table 1. Stages of Breast Cancer
|0||Tis, N0, M0|
|IA||T1, N0, M0|
|IB||T0 or T1, N1mi, M0|
T0 or T1, N1, M0
T2, N0, M0
T2, N1, M0
T3, N0, M0
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
|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).|
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.|
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.
|pNX||Regional lymph nodes cannot be assessed.|
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.
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.
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.
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.