by Jason Wasserman MD PhD FRCPC and Phil Williams MD FRCPC
January 5, 2025
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 often result in the tumour being subclassified as invasive ductal carcinoma or invasive lobular carcinoma.
Is invasive mammary carcinoma a type of 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 this diagnosis made?
The diagnosis of invasive mammary carcinoma is usually made after a small tumour sample is removed in a procedure called a biopsy. The tissue is then sent to a pathologist for examination under a microscope.
Immunohistochemistry
After diagnosing 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 e-cadherin and p120. In contrast, the tumour cells in invasive lobular carcinoma show weak or no expression of e-cadherin and intracytoplasmic (within the cell body) expression of p120.
Nottingham histologic grade
The Nottingham histologic grade is a system used to assess the aggressiveness of invasive mammary carcinoma by examining the cancer cells under a microscope. The grade is determined by looking at three specific features:
- Tubule formation: This refers to how much of the tumour is made up of round gland-like structures called tubules. Tumors with more tubule formation tend to be less aggressive.
- Nuclear pleomorphism: This describes how abnormal the cancer cell’s nucleus (the part of the cell that contains the DNA) looks compared to normal cells and how much variability there is between cells. The more abnormal it appears, the higher the grade.
- Mitotic rate: This measures how many cells in the tumour are dividing to form new cells. A higher number of mitotic figures suggests a more aggressive tumour.
Each of these features is given a score from 1 to 3, and the scores are added together to determine the final grade:
- Grade 1 (low grade): These tumours grow more slowly and are less likely to metastasize (spread) to lymph nodes.
- Grade 2 (intermediate grade): These tumours grow moderately and are more aggressive, with a higher risk of metastasizing to lymph nodes.
- Grade 3 (high grade): These tumours tend to grow quickly and are associated with a high risk of metastatic disease.
Breast cancer prognostic markers
Prognostic markers are proteins or other biological 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
ER (estrogen receptor) and PR (progesterone receptor) are proteins in some breast cancer cells. These receptors bind to the hormones estrogen and progesterone, respectively. When these hormones attach to their receptors, they can stimulate cancer cells to grow. The presence or absence of these receptors can classify invasive ductal carcinoma, which is important for determining treatment options and prognosis.
Why is the assessment of ER and PR important?
The presence of ER and PR in breast cancer cells means the cancer is hormone receptor-positive. This type of cancer is often treated with hormone (endocrine) therapy, which blocks the cancer cells’ ability to use hormones. Common hormone therapies include tamoxifen, aromatase inhibitors (such as anastrozole, letrozole, and exemestane), and drugs that lower hormone levels or block the receptors. Hormone receptor-positive cancers often respond well to these therapies.
Hormone receptor-positive breast cancers generally have a better prognosis than hormone receptor-negative cancers. They tend to grow more slowly and are less aggressive. Additionally, hormone receptor-positive cancers are more likely to respond to hormone therapies, which can reduce the risk of recurrence and improve long-term outcomes.
How are ER and PR assessed and reported?
ER and PR status is assessed through immunohistochemistry (IHC), performed on a tumour tissue sample obtained from a biopsy or surgery. The test measures the presence of these hormone receptors inside the cancer cells.
Here’s how the results are typically reported:
- Percentage of positive cells: Your report may include the percentage of cancer cells with ER and PR receptors. For example, a report might state that 80% of the tumour cells are ER-positive and 70% are PR-positive.
- Intensity of staining: The staining intensity (weak, moderate, or strong) reflects the number of receptors present in the nucleus of the cancer cells. This can help determine the likelihood of a response to hormone therapy.
- Allred score or H-score: Some reports may use a scoring system like the Allred score or H-score, which combines the percentage of positive cells and the intensity of staining to give an overall score. Higher scores indicate a higher likelihood that hormone therapy will be effective.
HER2
HER2, or human epidermal growth factor receptor 2, is a protein that is found on the surface of some breast cancer cells. It plays a role in cell growth and division. In some breast cancers, the HER2 gene is amplified, leading to an overproduction of the HER2 protein. This condition is referred to as HER2-positive breast cancer.
Why is the assessment of HER2 important?
HER2-positive breast cancers generally have a different prognosis compared to HER2-negative ones. Before the advent of targeted therapies, HER2-positive cancers were associated with a worse prognosis. However, with effective HER2-targeted treatments, the prognosis for these patients has improved significantly. Knowing the HER2 status also helps in planning the overall management of the disease. For instance, in addition to targeted therapy, HER2-positive patients might receive a combination of chemotherapy and other treatments tailored to their specific cancer profile.
How is HER2 assessed in invasive mammary carcinoma?
HER2 status is assessed through tests performed on a tumour tissue sample, which may be obtained through a biopsy or during surgery. The two main tests used are:
- Immunohistochemistry (IHC): This test measures the amount of HER2 protein on the surface of cancer cells. The results are reported as a score from 0 to 3+. A score of 0 or 1+ is considered HER2-negative, 2+ is borderline, and 3+ is HER2-positive.
- Fluorescence in situ hybridization (FISH): This test looks for the number of copies of the HER2 gene within the cancer cells. It is often used to confirm borderline IHC results. If the FISH test shows more copies of the HER2 gene than normal, the cancer is considered HER2-positive.
Other helpful resources
American Breast Cancer Foundation
Canadian Breast Cancer Foundation
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