by Jason Wasserman MD PhD FRCPC
April 4, 2022
Invasive ductal carcinoma is a type of breast cancer and the most common type of breast cancer to affect women worldwide. The tumour starts from cells normally found in the ducts and glands in the breast.
Some genetic syndromes are also associated with an increased risk of developing invasive ductal carcinoma. If you or a family member have been diagnosed with breast and ovarian cancer syndrome (BRCA1 and BRCA2), Cowden syndrome (PTEN), Peutz Jegher syndrome (STK11), or Li-Fraumeni syndrome (p53), you should talk with your doctor about your risk for developing breast cancer.
The diagnosis of invasive ductal carcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy. Tests for breast prognostic markers such as estrogen receptor (ER), progesterone receptor (PR), and HER2 may be performed on the biopsy and included in the biopsy report.
Surgery is then performed to remove the entire tumour which is sent to a pathologist for examination under the microscope. Depending on the amount of breast tissue removed, the surgery performed may be called a ‘lumpectomy’ (which means removal of the ‘lump’) or a ‘mastectomy’ which means removal of the entire breast.
After the tumour is removed it will be sent to a pathologist who will look for additional features such as the tumour size, tumour extension, lymphovascular invasion, perineural invasion, and the presence of tumour cells in lymph nodes. All of these features are described in more detail in the sections below.
Pathologists use a system called the Nottingham grading system to divide invasive ductal carcinoma into three levels or grades – 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:
The score from each category is added to determine the overall grade as follows:
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.
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 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:
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:
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.
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 cancer cells are found in either the skin or the muscles below the breast.
Tumour extension increases the tumour stage (see Pathologic stage below). 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.
Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels. Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.
Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.
Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.
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.
There are three types of lymph nodes that may be described in your report:
If cancer cells are found in a lymph node, the size of the area involved by cancer will be measured and described in your report as follows:
Finding cancer cells in a lymph node is associated with an increased risk that cancer will come back at a distant body site such as the lungs in the future. This information is also used to determine the nodal stage (see Pathologic stage below).
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. Margins will only be described in your report after the entire tumour has been removed.
A margin is considered 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.
A negative margin means 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. 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).
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:
Lymph nodes with cancer cells will also be examined for treatment effect.
The pathologic stage for 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.
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.
Ductal carcinoma is given a nodal stage between 0 and 3 based on the number of lymph nodes that contain cancer cells, the amount of cancer cells found in the lymph node, and the location of the lymph nodes with cancer cells.
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.