Breast Cancer

Staging

Breast cancer is classified according to the tumor, node and metastasis (TNM) system developed by the American Joint Committee on Cancer (AJCC) (see Table 1). Doctors categorize the tumor (T) according to its size and location, whether cancer cells are found in nearby lymph nodes (N) and whether the cancer has metastasized (M) to other parts of the body, such as the bones, brain, liver or lungs.

After breast cancer is classified, it is then staged (see Table 2). The stage is described by Roman numerals from 0 to IV and the letters A, B or C, if applicable. Stage 0 breast cancer refers to in situ breast cancer or noninvasive breast cancer, and Stage IV represents breast cancer that has spread beyond the breast and lymph nodes into distant organs. The staging system and prognostic stage also account for tumor size and nodal status.

These tables share information based on the size and spread of disease. Your final stage will be determined after your doctor also considers other factors, such as tumor grade and biomarker expression. These may include the most well-known biomarkers to guide breast cancer treatment, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status, as well as multi-gene panels, such as the Oncotype DX 21-gene recurrence score. Other panels such as MammaPrint, PAM 50 (Prosigna) and the Breast Cancer Index may also be considered for treatment planning.

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 breast cancer cells that carry the ER and/or PR biomarkers to “turn on” the growth of breast cancer cells. Breast cancers are classified according to the presence (ER+/PR+) or absence (ER-/PR-) of these receptors in the cells and the amount (or expression) of them. 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 hormone receptor or HER2 is referred to as triple negative breast cancer (TNBC).

Breast cancer is also classified into subtypes based on molecular or genetic changes. Identifying these subtypes 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 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 other cells in response to cancer as well as for genetic mutations.

Identifying hereditary breast cancer is also important in influencing treatment decisions. Patients who have inherited abnormalities in the breast cancer 1 (BRCA1) or breast cancer 2 (BRCA2) genes have an increased likelihood of developing breast cancer. 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. Furthermore, the presence of inherited mutations in the BRCA1 and BRCA2 genes or other cancer-susceptibility genes may influence decisions regarding cancer prevention (prophylactic) surgery. Talk with your doctor about your options before deciding if preventive surgery is right for you.

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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