- Cancer staging
- What is the TNM staging system?
- Modalities used to stage breast cancer
- Benefits and limitations of tumour staging
Staging is a method of categorising cancers based on their size, invasiveness and if they have spread to other sites in the body. This information can be used to quantify the prognosis (likely outcome), to determine the most suitable treatments for a particular individual, and to help compare treatment groups in clinical trials.
- Tumour (T): The extent of the primary tumour. For example, the size of the tumour, its type and/or invasiveness (direct spread into nearby structures);
- Nodes (N): The number and location of lymph nodes (collections of cells that act as a filter for the immune system) involved; and
- Metastases (M): If there are any distant metastases (spread of the tumour through the bloodstream to distant sites, for example breast cancer spreading through the blood to create a new tumour in a bone).
The TNM system is maintained and updated regularly by two bodies, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). The most recent revision is the seventh edition, and applies to all cancers diagnosed on or after 1 January 2010.
Once information about the primary tumour (T), lymph node involvement (N) and distant metastases (M) is gathered through clinical, radiological and pathological examination (see below), the tumour can be given a grade based on the individual components T, N and M.
The first section of the TNM staging system refers to the primary tumour. The designation (in bold) is based on the greatest diameter of the primary tumour, its invasiveness and also the type of tumour.
|TX||Assessment of the primary tumour cannot be made.|
|T0||No evidence of the primary tumour.|
|T1||Tumour ≤ 20 mm in greatest dimension. This can be further classified according to size.|
|T2||Tumour > 20 mm but ≤ 50 mm in greatest dimension.|
|T3||Tumour > 50 mm in greatest dimension|
|T4||Any size tumour that demonstrates direct extension (invasion) into the chest wall and/or to the skin. This can be further classified.|
|Tis||Carcinoma in situ.|
|Tis (DCIS)||Ductal carcinoma in situ (where the cancer cells resemble that of the breast ducts)|
|Tis (LCIS)||Lobular carcinoma in situ (where the cancer cells resemble that of the breast glands or lobules).|
|Tis (Paget’s)||Paget’s disease of the nipple (an uncommon breast cancer forming in or around the nipple) NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast tissue.|
|For more information on the breast, see Anatomy of the Breast.|
The second component of the TNM staging system refers to the involvement of lymph nodes. Designations are again in bold.
|NX||Assessment of regional lymph nodes cannot be made (e.g. previously removed).|
|N0||No regional lymph node involvement.|
|N1||Involvement of lymph nodes in the axilla (arm pit) on the same side as the primary tumour. The lymph nodes affected are still moveable and not anchored to surrounding tissue.|
|N2||Involvement of lymph nodes in the axilla on the same side as the primary cancer that are fixed to surrounding structures OR where internal mammary nodes on the same side as the primary tumour are involved without evidence of lymph nodes in the axilla being affected.|
|N3||Involvement of lymph nodes that lie above or below the clavicle bone (collar bone) OR those affecting both mammary lymph nodes and lymph nodes in the axilla on the same side as the primary tumour.|
Where tissue has been removed by surgery and investigated by a pathologist, further classifications can be given. This is denoted by the prefix p.
The final component of the TNM staging system is dependent on whether there is any evidence for metastases to distant sites.
|M0||No clinical or radiographic evidence of distant metastases.|
|cM0(i+)||No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumour cells in circulating blood, bone marrow, or other non-regional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases.|
|M1||Distant detectable metastases as determined by classic clinical and radiographical means and/or histologically proven to be larger than 0.2 mm.|
Once information is gathered pertaining to T, N, and M, this can be used to determine the stage as outlined below:
|Stage 0||Tis N0 M0|
|Stage IA||T1 N0 M0|
|Stage IB||T0 N1 M0|
T1 N1 M0
|Stage IIA||T0 N1 M0|
T1 N1 M0
T2 N0 M0
|Stage IIB||T2 N1 M0|
T3 N0 M0
|Stage IIIA||T0 N2 M0|
T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
|Stage IIIB||T4 N0 M0|
T4 N1 M0
T4 N2 M0
|Stage IIIC||Any T N3 M0|
|Stage IV||Any T Any N M1|
From this we can see that any cancer that has given rise to distant metastases is stage IV, and any tumour less than 20 mm in maximal diameter without lymph node involvement or distant metastases is stage IA.
Staging of a breast cancer involves clinical, radiological and pathological examinations.
Clinical examination includes history taking, physical examination and laboratory investigations.
History taking should be comprehensive and include:
- Complete medical history;
- Family history of breast, ovarian and other cancers;
- Current function to determine performance status (a measure of wellbeing); and
- Menopausal status.
- Palpation of both breasts (the breasts are observed and felt in a systemised way to detect any breast lumps); and
- Palpation of local regional lymph nodes, for example those in the arm pit or surrounding the clavicle (collar bone).
Investigations should include:
- Full blood picture: A blood test that reports the number of red and white blood cells;
- Liver function test: To assess if liver function is affected by cancer spreading to the liver;
- Renal function tests: To determine the satisfactory function of the kidneys;
- Alkaline phosphatase levels: If high, it may indicate the possibility of cancer spreading to bone; and
- Calcium levels: If high, it may indicate the possibility of cancer spreading to bone.
If menopausal status is uncertain, it should be clarified, as it can affect which treatments are offered.
Magnetic resonance imaging (MRI) is not routinely used but can be useful in certain situations, including for younger women with dense breast tissue, those with familial breast cancer, those in which secondary spread to lymph nodes is observed but there is no identifiable primary tumour, or if the doctor suspects multiple tumour sites.
Other imaging to exclude metastases may be performed, including:
- Chest x-ray;
- Abdominal ultrasound; and/or
- Bone scan.
Patients with early stage breast cancer N0 do not benefit from extensive radiological investigations.
Pathological investigations include samples from fine needle aspiration (where a needle is introduced to collect a sample), core needle biopsy (a larger needle is used for a more complete sample) or complete surgical specimens (those removed by surgery).
The information gained from fine needle aspiration and core needle biopsy includes the type and grade of the cancer as well as determination of oestrogen receptor, progesterone receptor and HER2 receptor status, which can affect what treatments are offered.
Evaluation of surgical specimens usually includes:
- The number, location and maximum diameter of all tumours resected (removed);
- Evaluation of the resection margin (i.e. how much normal tissue has been removed along with the tumour);
- Presence of invasion into blood vessels or lymphatic system;
- Determination of oestrogen, progesterone and HER2 receptor status;
- The total number of lymph nodes removed, and the number of these that are positive; and
- For tumour-positive lymph nodes, the extent of the metastases should be described, including isolated tumour cells, micrometastases (0.2–2 mm), or macrometastases.
The benefit of a staging system is that it is a structured method of describing the anatomical extent of a cancer, which can then be used to provide information about the prognosis, direct treatment, assess the chance of successful treatment outcomes, or help compare treatment groups in clinical trials.
However, with advances in molecular biological techniques, our understanding of breast cancer is no longer one of a single disease entity. There are many different subtypes of breast cancers that may behave differently to each other. While the latest edition of the TNM staging system has tried to incorporate differences in biology, some cancers may show little correlation between the tumour stage and the clinical outcome.
The main reason for staging cancers is to provide a means to quantify prognosis and provide appropriate treatment strategies for optimal patient outcomes. To illustrate this, tumours greater than 4 cm in diameter or with many sites would not be candidates for breast conserving therapy, an alternative that offers more cosmetic results than does mastectomy. Post-operative radiotherapy would be recommended for most women undergoing breast conserving therapy; for those undergoing mastectomy, it would only be recommended for patients with T3–T4 tumours ,or those where the cancer has spread to the lymph nodes in the axilla or beyond. Patients with oestrogen receptor positive breast cancers can be treated with tamoxifen (sold as Tamoxen or Genox); those with cancers that lack the hormone receptors should not receive endocrine therapy. Having a widely accepted and used staging system gives clinicians the means to describe the anatomical extent and biology of breast cancers, and so direct the most appropriate therapies for women with breast cancer.
For more information on breast cancer, types of breast cancer and its investigations and treatments, as well as some useful videos, see Breast Cancer.
Kindly written by:
Dr Allison Johns
BSc (Biomed/Mol Biol) Hons, MBBS
Doctor, Royal Perth Hospital, and Editorial Advisory Board member of the Virtual Medical Centre
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