The TNM Breast Cancer Staging: Section 7.a.

 
CONTENTS:
 
7.1 The AJCC TNM Categories for Breast Cancer Staging Categories
7.1.1 The T Categories
7.1.2 The N Categories
i. The Clinical Classification of Regional Lymph Nodes
ii. The Pathologic Classification of Regional Lymph Nodes
7.1.3 The M Categories
7.2 Summary of the Stage I to IV Categories
 

This page is 7A breast cancer staging. Forward to 7B breast cancer staging. Back to section 6D about triple negative tests.

Breast cancer is diagnosed and graded using light microscopy, and prognostic and predictive tissue markers are analyzed on the breast tumor tissue.

The next part of the diagnostic process is breast cancer staging. Staging involves assessment of the size of the primary cancer and determination of local and distant metastases (spread).

Somebody stole my mood ring. Now I really don’t know how I feel about that.

The TNM Breast Cancer Staging System

 
The ‘Tumor-Node-Metastasis’ (TNM) staging system for breast cancer classifies breast cancer for treatment purposes on the basis of the primary tumor type (invasive or in-situ) and size (T), the presence or absence of regional lymph node spread (N), and the presence or absence of distant metastases (M). The overall Stage of breast cancer (stage I through IV) results from the combination of T, N, and M characteristics.

The TNM staging system may estimate patient survival.  However, medical specialists will not use this method alone to dictate treatment.  As there are advancements in imaging techniques and treatments, revision of the staging guidelines will also be necessary.

The most recent version of the TNM breast cancer staging system is the 7th edition of the American Joint Committee on Cancer (AJCC) ‘TNM Classification of Malignant Tumors.’ These revised Staging guidelines became effective from January 1st, 2010 and include new tumor stage groupings and some refinements of the previous T and M descriptors.

Why do they keep changing the TNM classification system?

I’m glad they do, and it shows that breast cancer experts are active and progressive. Some other kinds of cancer have TNM based on decades-old beliefs.

The AJCC Poster Summary of TNM Breast Cancer Staging

 
The American Joint Committee on Cancer (AJCC) has also produced a two-page PDF poster to summarize breast cancer staging for patients.

At the end of this section, there is a list of key references to the  literature, with links to access the articles. There are also some helpful links to patient websites and to sources of further information.

If you’ve been newly diagnosed, or are facing breast cancer staging information, remember it’s only when the sun goes down that the stars come out.

No Brittany, I prefer my personal motto which is…when all else fails, take a nap!

7.1 The AJCC Staging Categories for Breast Cancer

 
The letters TNM describe three aspects of the staging process:-

• The size of the primary breast tumor (T)
• Presence or absence of metastasis (cancer spread) to regional lymph nodes (N)
• The presence or absence of distant metastases (M)

The TNM scores classify the tumor from Stage 0 (the lowest stage) to Stage IV (the most advanced stage).  Modifications to this classification can include P factors from the Pathologist.

We should go for a run after this.

Did you know I’ve been hiding from exercise for a while now in the Fitness Protection Program?

the American Joint Committee on Cancer (AJCC) reviews and develops the TNM classifications (AJCC Staging Manual, 7th Edition) and the latest guidelines are from 2010.

7.1.1 The T Categories

 
In the TNM staging system, T categories refer to the primary breast tumor and the local spread within the breast.

• TX:      Assessment of the primary tumor is not possible
• T0:      There is no evidence of primary tumor
• Tis:     Carcinoma in-situ, the earliest stage of cancer or non-invasive breast cancer
• Tis (DCIS) – Ductal carcinoma in-situ.
• Tis (LCIS) – Lobular carcinoma in-situ.
• (Paget’s) Tis – Paget’s disease of the nipple is present but not associated with underlying invasive carcinoma and/or carcinoma in-situ (DCIS and/or LCIS). If an underlying breast carcinoma is present, the physician categorizes it according to the size and characteristics of the tumor.   However, the pathologist should still not the presence of Paget disease.

I still haven’t got to grips with the difference between ductal and lobular breast cancers.

Ductal carcinoma in situ (DCIS) refers to abnormal cells that are inside a milk duct in the breast and Lobular carcinoma in situ (LCIS) refers to abnormal cells in the lobules or milk glands in the breast. ‘In-situ’ means in it’s original place or that the cancer is contained.

Ah now I see, and Tis stands for ‘in-situ’- the cancer cells have stayed in the place where they began.

T1 to T4

 
T1:      The tumor is ≤2 cm. This category includes T1mic, an area of micro-invasion in which the invasive tumor is ≤0.1cm.

• T1a – Tumor >1 mm but ≤5 mm in greatest dimension.
• T1b – Tumor >5 mm but ≤10 mm in greatest dimension.
• T1c – Tumor >10 mm but ≤20 mm in greatest dimension.

• T2:      The tumor is >2cm to ≤5cm.
• T3:      The tumor is >5cm
• T4:      A tumor is of any size but has spread to the chest wall or breast skin

• T4a – Extension to the chest wall.
• T4b – Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d’orange) of the skin (but which do not meet the criteria for inflammatory breast carcinoma).
• T4c – Both (T4a and T4b)
• T4d – Inflammatory breast carcinoma, with skin changes, involving a third or more of the skin of the breast. While the histologic presence of invasive carcinoma invading dermal lymphatics is supportive of the diagnosis, it is not actually necessary.

Ooooh la la, très française. What is ‘peau d’orange’, is it a fancy French dessert?

No, It means that the skin of the breast has an orange peel appearance, ‘peau d’orange’ literally means ‘skin of orange’.

7.1.2 The N Categories

 
Lymph node classification criteria differ depending on whether the nodes are clinically or pathologically assessed.

To make the distinction between clinical or pathological assessment of lymph nodes, there is a designation of cN or pN

Pathologic classification is preferable to clinical assessment, when available.

The clinical classification should reflect the clinical assessment and imaging studies. The pathologic classification is essentially what the pathologists sees in the lymph nodes that were removed at surgery.

The pathologic stage can be different from the clinical stage, for example, if surgery shows the cancer has spread more than it was thought before surgery. The pathological stage gives the health care team more precise information that can be used to predict treatment, response and prognosis.

Regional lymph nodes include axillary nodes, ipsilateral intra-mammary nodes, internal mammary nodes and supraclavicular nodes.   So, within the breast tissue itself are the intra-mammary lymph nodes.  The pathologist codes these lymph nodes as ‘axillary lymph nodes’ for staging purposes. In addition, the pathologist classifies supraclavicular lymph nodes as ‘regional lymph nodes’ for staging purposes.

Metastases to any other lymph nodes, including cervical, or contralateral axillary lymph nodes are classified as ‘distant’ (M1).

Gosh! there are a lot of different types of regional lymph nodes, but what does that mean?

Imaging studies show the regional lymph nodes that are around the affected breast.  Cervical lymph nodes are located in the neck and contralateral lymph nodes are on the opposite side of the body. Which lymph nodes have been affected, and how far away, or distant, they are to the primary cancer is an important staging factor.

i. The Clinical Classification of Regional Lymph Nodes

 
Lymph flow from the deep subcutaneous and intra-mammary vessels moves centrifugally toward the axillary and internal mammary lymph nodes. The majority (98 %) of the lymph flows to the axillary nodes.

Section 6 has described the examination of the sentinel lymph node (SLN) and the search for micro-metastases, which are important in clinical staging for breast cancer (Cserni et al., 2004).

The clinical nodal or N classification reflects what is clinically palpatable or shows on imaging studies.

Does running late count as exercise?

• cNX:   It is not possible to assess regional lymph nodes
• cN0:    No regional lymph node metastases




• cN1:    Metastasis to movable ipsilateral Level I, II axillary lymph nodes(s)
• cN2:    Metastasis to ipsilateral Level I, II axillary lymph nodes that are clinically fixed or matted; or in clinically detected ipsilateral internal mammary nodes in the absence of clinically evident axillary node metastases

cN2a to cN3b

• cN2a: Metastasis to ipsilateral level I, II axillary lymph nodes fixed to one another or to other structures
• cN2b: Metastasis only in clinically detected ipsilateral internal mammary nodes, and in the absence of clinically evident axillary node metastases

All this is giving me a bit of a headache. So, what exactly are the ipsilateral level I, II and III axillary lymph nodes?  Wow, what a mouthful!

Ipsilateral means on the ‘affected side’.  So, specialists describe the levels of the axillary lymph nodes in relation to the pectoralis minor muscle.  Thus, level I nodes are situated to the lateral border of the muscle, level II are situated behind the muscle and level III are situated internally to the muscle.

cN3:    Metastases in ipsilateral infraclavicular (Level III axillary) lymph node(s) with or without Level I, II axillary lymph node involvement; or in clinically detected ipsilateral internal mammary lymph node(s) with clinically evident Level I, II axillary lymph node metastases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement

• cN3a: Metastasis to ipsilateral infraclavicular lymph node(s)
• cN3b: Metastasis to ipsilateral internal mammary lymph node(s) and axillary lymph nodes

Above was Clinical. Here is Pathological. In other words, Above is used before they have biopsy proof, Here in pathology is after they have biopsy proof, which is better.

ii. The Pathologic Classification of Regional Lymph Nodes

 
The pathologic classification follows surgical removal of regional lymph nodes and histological reporting by the Pathologist.

• pNX:   The assessment of regional lymph nodes is not possible

• pNO: No regional lymph node metastasis is histologically present

• pNO(i-): No regional lymph node metastases are present on histology, in addition,  IHC is negative.
• pN0(i+): Malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC).
• pNO(mol-): No regional lymph node metastases seen histologically and negative molecular findings (RT-PCR), no metastases detected by histology or IHC.
• pNO (mol+): Positive molecular findings (RT-PCR), but histology and IHC detects no regional lymph node metastases.

This is quite heavy going, what is IHC again?

Incredible Hector Charm.

It’s ‘What they saw in the microscope‘, when the pathologist used ImmunoHistoChemistry to stain the microscope slide tissue specimen.

pN1 to pN2b

• pN1:    Micro-metastases, or metastases in one to three axillary lymph nodes, and/or in internal mammary nodes with metastases detected by sentinel lymph node (SLN) biopsy but are not clinically detected

• pN1mi: Micro-metastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm).
• pN1a: Metastases in 1 to 3 axillary lymph nodes, at least one metastasis greater than 2.0 mm.
• pN1b: Metastases in internal mammary nodes with micro-metastases or macro-metastases detected by sentinel lymph node (SLN) biopsy but not clinically detected.

When I see lover’s names carved on trees, I don’t think it’s sweet. I just think how strange it is that so many people bring knives on a date.

• pN2: Metastases in four to nine axillary lymph nodes, or in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases

• pN2a: Metastases in four to nine axillary lymph nodes (at least one tumor deposit greater than 2.0 mm).
• N2b: Metastasis only in clinically detected ipsilateral internal mammary nodes and in the absence of clinically evident axillary node metastases.
• pN2b: Metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases.

This is all very complicated, one of my headaches is starting.

Well, if you are agitated and confused our work here is done!

pN3 Metastases

 
pN3: Metastases is present in 10 or more axillary lymph nodes, or in infraclavicular (Level III axillary) lymph nodes.   Also, if a pathologist detects metastases in the ipsilateral internal mammary lymph nodes.  Furthermore, the presence of 1 or more positive Level I, II axillary lymph nodes.  PN3 is also the classification if metastases is present in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micro-metastases or macro-metastases detected by sentinel lymph node (SLN) biopsy but not clinically detected; or in ipsilateral supraclavicular lymph nodes

pN3a to pN3b

• pN3a: Metastases in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm); or metastases to the infraclavicular (Level III axillary lymph nodes).
• pN3b: Metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive axillary lymph nodes; or in more than three axillary lymph nodes and in internal mammary lymph nodes with micro-metastases or macro-metastases detected by sentinel lymph node (SLN) biopsy but not clinically detected.

There’s so much information just in the pathology report alone after surgery.

Yes, it’s true, but the key is not to focus too much on any one piece of information. Wait until you have all the relevant information and then you and your doctor can make informed decisions together about treatment.

Specialists define isolated tumor cell clusters (ITC)  as, ‘small clusters of cells not greater than 0.2 mm,’ or ‘single tumor cells,’ or a ‘cluster of fewer than 200 cells’ in a single histologic cross-section.’ Routine histology tests or the use of immunohistochemical (IHC) may detect ITC’s.

Figure 7.1 Lymph Node Metastases and ITC&lt

Photomicrograph of the histology of a sentinel lymph node (SLN) from the axilla
shows that metastatic breast cancer replaces most of the node.  (H&E x 20)
B. Photomicrograph of the immunohistochemistry (IHC) for cytokeratin markers
(brown) of an axillary lymph node shows localization of cell membrane staining
to a small cluster of carcinoma cells; this is an ‘isolated tumor cell cluster’
(ITC). (Cam5.2 IHC x 60)

Not Clinically Detected

 
N classification, excludes lymph nodes containing only Isolated Tumor Cells (ITCs) from the total positive node count.  However, the pathologist will include ITC’s in the total number of nodes that he evaluates.

The definition of ‘not clinically detected‘ is that a breast cancer specialist does not detect an abnormality on either imaging studies (excluding lymphoscintigraphy) or by clinical examination.

The definition of ‘Clinically detected’ is when a breast cancer specialist detects an abnormality on imaging studies (excluding lymphoscintigraphy) or by clinical examination.  Furthermore, the abnormality has characteristics that are ‘highly suspicious for malignancy‘ or the specialist presumes that pathologic macro-metastasis from fine needle aspiration (FNA) with cytologic examination.

Waiting for biopsy results and staging information is a very stressful time, but remember hope, and hope is being able to see that there is light despite all of the darkness.

Metastasis

 
Confirmation of clinically detected metastatic disease by fine needle aspiration (FNA) without excision biopsy is designated with an (f) suffix, for example, cN3a(f).

Excisional biopsy of a lymph node or biopsy of a sentinel lymph node (SLN), in the absence of assignment of a pT, is classified as a clinical N, for example, cN1.

Information regarding the confirmation of the nodal status will be designated in site-specific factors as clinical, fine needle aspiration, core needle biopsy (CNB), or sentinel lymph node (SLN) biopsy.

Pathologic classification (pN) is used for excision or sentinel lymph node (SLN) biopsy only in conjunction with a pathologic T assignment.

7.1.3 The M Categories

 
The M categories document whether there is breast cancer metastasis (spread) to distant sites (tissues or organs).

• MX:    Insufficient information to describe the spread of the cancer
• M0:     No distant metastasis found

• cMO(i+): No clinical or radiographic evidence of distant metastases, but deposits of microscopically-detected cancer cells in circulating blood (circulating tumor cells or CTCs), bone marrow or other non-regional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastatic disease.
• M1:     Distant metastases are present

7.2 Summary of the Stage 0 to IV Categories

 
Sometimes, the patient with a diagnosis of breast cancer will receive a staging diagnosis using the Stage O to IV categories.

So, the table below is a summary of the TNM categories:-
 
T4 N0 M0 T4 N1 M0 T4 N2 M0

References:

 
Cserni, G., Bianchi, S., Boecker, W., et.al. (2004). Improving the reproducibility of diagnosing micrometastases and isolated tumor cells. Oncology and Radiotherapy. Vol 103 Issue 2. (Retrieved November 26^th 2014): https://www.ncbi.nlm.nih.gov/pubmed/15593354

American Cancer Society: Cancer Facts and Figures 2014. Atlanta: American Cancer Society. (Retrieved 23^rd October 2014): https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2014.html

AJCC (American Joint Committee on Cancer). Cancer Staging Manual, 7th Edition. Edge SB, Byrd DR, Compton CC, et al (Eds), Springer-Verlag, New York 2010. p.347.

More references for this section are on this page.

Patient Information:

American Cancer Society. Staging (Retrieved December 16^th2014): 2014): http://www.cancer.org/treatment/understandingyourdiagnosis/staging

NCCN National Cancer Institute. Stage Information for Breast Cancer; Definitions of TNM and AJCC Stage Groupings (Retrieved October 29^th 2014): http://www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional/page3#_695_toc

More patient information for this section is on this page.

This page is 7.A breast cancer staging. Forward to 7.B breast cancer staging Back to 6D on triple negative tests.