by Jason Wasserman MD PhD FRCPC and Phil Williams MD FRCPC
July 24, 2023
What is invasive mammary carcinoma?
Invasive mammary carcinoma is a diagnosis used to describe a cancerous tumour in the breast that has not been subclassified into a more specific type of breast cancer. Additional tests performed often result in the tumour being subclassified as invasive ductal carcinoma or invasive lobular carcinoma.
Is invasive mammary carcinoma the same as breast cancer?
Yes. Invasive mammary carcinoma is a term that describes a group of related breast cancers.
What are the most common subtypes of invasive mammary carcinoma?
The most common subtypes of invasive mammary carcinoma are invasive ductal carcinoma and invasive lobular carcinoma.
How is the diagnosis of invasive mammary carcinoma made?
The diagnosis of invasive mammary 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.
How does immunohistochemistry help with the diagnosis?
After making the diagnosis of invasive mammary carcinoma, your pathologist may order a test called immunohistochemistry to help further subclassify the tumour into invasive ductal carcinoma or invasive lobular carcinoma. When immunohistochemistry is performed, two markers are typically assessed: e-cadherin and p120. The tumour cells in invasive ductal carcinoma usually show strong membranous expression of both e-cadherin and p120 while the tumour cells in invasive lobular carcinoma show weak or no expression of e-cadherin and intracytoplasmic (within the cell body) expression of p120.
What is the Nottingham histologic grade for invasive mammary carcinoma and why is it important?
The Nottingham histologic grading system is used to divide invasive mammary 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.
How do pathologists determine the Nottingham grade for invasive mammary carcinoma?
The Nottingham grade can only be determined after the tumour is examined under the microscope. When examining the tumour, pathologists look for the following three microscopic features:
- 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.
- 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 of 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.
- 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.
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.
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