Invasive ductal carcinoma (IDC) of the breast

by Jason Wasserman MD PhD FRCPC
June 3, 2022


What is invasive ductal carcinoma of the breast?

Invasive ductal carcinoma (IDC) is a type of breast cancer and the most common type of breast cancer worldwide. Another name for this type of cancer is infiltrating ductal carcinoma.

How is the diagnosis of invasive ductal carcinoma made?

The diagnosis of invasive ductal carcinoma is usually made after a small sample of the tumour is removed in a procedure called a biopsy. The tissue is then sent to a pathologist for examination under a microscope. The biopsy report may also include the histologic grade and breast prognostic markers such as estrogen receptor and progesterone receptor. After the diagnosis is made, most patients undergo a second surgical procedure to remove the entire tumour.

What is the Nottingham histologic grade for invasive ductal carcinoma?

The Nottingham histologic grading system is used to divide invasive ductal carcinoma into three levels or grades numbered 1, 2, and 3. The grade is important because grade 2 and grade 3 tumours tend to grow more quickly and are more likely to spread to other parts of the body such as lymph nodes.

The Nottingham grade can only be determined after the tumour is examined under the microscope. When examining the tumour, pathologists look for the following four microscopic features:

  1. Tubules  – A tubule is a group of cells connected together to form a round, ring-like structure. Tubules look similar but are not exactly the same as the glands that are normally found in the breast. A score of 1 to 3 is given based on the percentage of cancer cells forming tubules. Tumours made up mostly of tubules are given a score of 1 while tumours made up of very few glands are given a score of 3.
  2. Nuclear pleomorphism – The nucleus is a part of the cell that holds most of the genetic material (DNA). Pleomorphism (or pleomorphic) is a word pathologists use when the nucleus of one tumour cell looks very different from the nucleus in another tumour cell. A score of 1 to 3 is given for nuclear pleomorphism. When most of the cancer cells are small and look very similar to each other, the tumour is given a score of 1. When the cancer cells are very large and abnormal-looking, the tumour is given a score of 3.
  3. Mitotic rate – Cells divide in order to create new cells. The process of creating a new cell is called mitosis, and a cell that is dividing is called a mitotic figure. Your pathologist will count the number of mitotic figures in a specific area (called a high-powered field) and will use that number to give a score between 1 and 3. Tumours with very few mitotic figures are given a score of 1 while those with many mitotic figures are given a score of 3.​

The score from each category is added to determine the overall grade as follows:

  • Grade 1 – Score of 3, 4, or 5.
  • Grade 2 – Score of 6 or 7.
  • Grade 3 – Score of 8 or 9.
What are breast prognostic markers?

Prognostic markers are proteins or other biologic elements that can be measured to help predict how a disease such as cancer will behave over time and how it will respond to treatment. The most commonly tested prognostic markers in the breast are the hormone receptors estrogen receptor (ER) and progesterone receptor (PR) and the growth factor HER2.

Hormone receptors

ER and PR are proteins that allow cells to respond to the actions of the sex hormones estrogen and progesterone. ER and PR are made by normal breast cells and by some breast cancers. Cancers that make ER and PR are described as ‘hormone sensitive’ because they depend on these hormones to grow.

Your pathologist will perform a test called immunohistochemistry to see if the cells in the tumour are making ER and PR. This test is often performed on the biopsy sample. However, in some situations, it may only be performed after the entire tumour is removed.

Pathologists determine the ER and PR score by measuring the percentage of tumour cells that have protein in a part of the cell called the nucleus and the intensity of the stain. Most reports give a range for the percentage of cells that show nuclear positivity while the intensity is described as weak, moderate, or high.

HER2

HER2 is a protein that is made by normal, healthy cells throughout the body. The tumour cells in some types of cancer make extra HER2 and this allows the cells in the tumour to grow faster than normal cells.

There are two tests that are commonly performed to measure the amount of HER2 in tumour cells. The first test is called immunohistochemistry and it allows your pathologist to see the HER2 protein on the surface of the cell. This test is given a score of 0 through 3.

HER2 immunohistochemistry score:

  • Negative (0 and 1) – A score of 0 or 1 means the tumour cells are not making extra HER2 protein.
  • Equivocal (2) – A score of 2 means the cells may be making extra HER2 protein and another test called fluorescence in situ hybridization (see below) will need to be performed to confirm the results.
  • Positive (3) – A score of 3 means the cells are making extra HER2 protein.

The second test that is used to measure HER2 is called fluorescence in situ hybridization (FISH). This test is usually only performed after a score of 2 on the immunohistochemistry test. Instead of looking for HER2 on the outside of the cell, FISH uses a probe that sticks to the HER2 gene inside the nucleus of the cell. Normal cells have 2 copies of the HER2 gene in the nucleus of the cell. The purpose of the HER FISH test is to identify tumour cells that have more copies of the HER2 gene which allows them to make more copies of the HER2 protein.

Tumour cells that make extra HER2 will also have more DNA instructions for HER2. Pathologists call this change a translocation.

HER2 FISH score:

  • Positive (amplified) – The tumour cells have extra copies of the HER2 gene. These cells are most likely making extra HER2 protein.
  • Negative (not amplified) – The tumour cells do not have extra copies of the HER2 gene. These cells are most likely not making extra HER2 protein.

What is ductal carcinoma in situ (DCIS)?

Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer. Over time, DCIS can turn into invasive ductal carcinoma. For this reason, DCIS is often seen in the tissue surrounding invasive ductal carcinoma and when it is seen, it will be included in your pathology report. In contrast to invasive ductal carcinoma, the tumour cells in DCIS are only seen inside ducts and not in the surrounding stroma.

Has the tumour spread into any tissues outside of the breast?

Invasive ductal carcinoma starts inside the breast but the tumour may spread into the overlying skin or the muscles of the chest wall. The term tumour extension is used when tumour cells are found in either the skin or the muscles below the breast.

Tumour extension is important because it increases the pathologic tumour stage (pT). It is also associated with a higher risk that the tumour will grow back after treatment (local recurrence) or that cancer cells will travel to a distant body site such as the lung. The spread of cancer cells to another part of the body is called metastasis.

What is lymphovascular invasion?

The term lymphovascular invasion is used to describe tumour cells found inside a blood or lymphatic vessel. Blood vessels are long, thin, hollow tubes that carry blood around the body. Lymphatic vessels are similar, however, instead of carrying blood, they contain waste and immune cells. Once tumour cells are inside a blood or lymphatic vessel, they are able to metastasize (spread) to other parts of the body such as lymph nodes. For this reason, lymphovascular invasion is associated with an increased risk of developing metastatic disease.

lymphovascular invasion

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs located throughout the body. For patients diagnosed with invasive ductal carcinoma, lymph nodes are often removed to look for cancer cells that may have spread from the tumour to the lymph node. The examination of lymph nodes is important because it is used to determine the pathologic nodal stage (pN).

Lymph node

There are three types of lymph nodes that may be described in your report:

  • Sentinel axillary lymph nodes – This is the first lymph node in the chain of lymph nodes that drains fluid from the breast. If cancer is going to be found in the axilla, it will usually be found in the sentinel node first.
  • Non-sentinel axillary lymph nodes – This type of lymph node is located after the sentinel lymph node in the axilla. Cancer cells usually travel to these lymph nodes after passing through the sentinel lymph node.
  • Internal mammary lymph nodes – This type of lymph node is found in the breast itself. Cancer cells may travel to these lymph nodes if the lymph node is found close to the tumour.

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells. If cancer cells are found in a lymph node, the size of the area involved by cancer will also be measured and described in your report as follows:

  • Isolated tumour cells – The area of cancer cells measures less than 0.2 millimetres and have less than 200 tumour cells.​
  • Micrometastases – The area of cancer cells measures more than 0.2 millimetres but less than 2 millimetres.
  • Macrometastases – The area of cancer cells measures more than 2 millimetres.
What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed.

Your pathologist will carefully examine all the margins in your tissue sample to see how close the cancer cells are to the edge of the cut tissue. Your report will only describe margins after the entire tumour has been removed.

Margin

A margin is called negative if there were no cancer cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will say how far the closest cancer cells were to a margin. A margin is called positive when there are cancer cells at the very edge of the cut tissue. If ductal carcinoma in situ (DCIS) is seen at the edge of the cut tissue that will also be described in your report. The distance is usually described in millimetres. A positive margin is associated with a higher risk that the tumour will grow back in the same site after treatment (local recurrence).

What does treatment effect mean?

If you received treatment (either chemotherapy or radiation therapy) for your cancer prior to the tumour being removed, your pathologist will examine all of the tissue submitted to see how much of the tumour is still alive (viable).

The treatment effect will be reported as follows:

  1. No residual tumour – all the cancer cells are dead
  2. Probable effect – some of the cancer cells are dead but some are still alive
  3. No definitive response – most of the cancer cells are still alive

Lymph nodes with cancer cells will also be examined for treatment effects.

How is invasive ductal carcinoma of the breast staged?

​The pathologic stage for invasive ductal carcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for invasive ductal carcinoma

Invasive ductal carcinoma is given a tumour stage between T1 and T4 based on the size of the tumour and the presence of cancer cells in the skin or muscles of the chest wall.

breast cancer pathologic stage

Nodal stage (pN) for invasive ductal carcinoma

Invasive ductal carcinoma is given a nodal stage between 0 and 3 based on the number of lymph nodes that contain cancer cells, the number of cancer cells found in the lymph node, and the location of the lymph nodes with cancer cells.​

Metastatic stage (pM) for invasive ductal carcinoma

Invasive ductal carcinoma is given a metastatic stage of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely sent, the metastatic stage cannot be determined and is listed as pMX.

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