Breast cancer types

Breast cancer is a very heterogeneous disease, which means that each case is different. Determining the type of cancer is key to making the best possible choice of treatment. Diagnostic tests are used to characterize the breast cancer according to several criteria:  

• Tumour location
• Stage and migratory state
• Tumour grade
• Molecular subtype  
• Rare types of breast cancer: inflammatory, Paget’s disease, metaplastic, etc. 
• Gene mutations  

There are over 150 combinations of these factors, each with its own risk of progressing, metastasizing and recurring. An adapted treatment plan can be established by considering these different factors, which vary from one breast cancer to another.   

Breast cancer characterization takes into account the location of the cancer cells. Breast cancer can develop in different structures in the breast:  

• Ductal carcinoma: cancer cells are present in the lactiferous ducts (small ducts that transport milk). This type represents 85% of breast cancers. 
• Lobular carcinoma: cancer cells are present in the lobules (the small structural units that make up the breast). This type represents 10–15% of breast cancers.  

The stage is measured from 0 to 4, and determines the scope of the breast cancer. Depending on the stage, the breast cancer is considered in situ, early, locally advanced or metastatic (advanced).

The TNM (Tumour, Node, Metastasis) system is used to determine the stage of the cancer. This evaluation takes into account the size of the tumour, the number of lymph nodes containing cancer cells and the presence of cancer in other organs.

Stage	Characteristics	Migratory status
0	The cancer cells are located only within the membrane of the lactiferous duct (i.e., ductal carcinoma in situ) or lobule (i.e., lobular carcinoma in situ) in which they emerged.	In situ (non-invasive): The cancer cells remain in the place where they emerged without invading nearby tissues.
1	The cancerous tumour is 2 cm or less in size and has not spread to the lymph nodes or only a few cancer cells are observed in the nodes.	Infiltrating (invasive): The cancerous tumour may break the membrane of the tissue in which it developed. Cancer cells have left the tissue in which they developed and are located in nearby tissues.
2	The cancerous tumour is more than 2 cm in size and has not spread to nearby lymph nodes, or it measures less than 5 cm but has spread to nearby nodes.
3	The cancer has spread to the lymph nodes and possibly to nearby tissues, such as muscles or skin.
4	The cancer has spread to other parts of the body, in distant organs.	Metastatic: Cells travel through the bloodstream or lymphatic system to spread and attach themselves to other organs (Stage 4).

The grade, on a scale from 1 to 3, measures the degree of malignancy, i.e., the speed of spread, of the breast cancer. The higher the grade, the faster the cancer cells are likely to develop and the more likely they are to spread compared to low-grade cells.  

The pathologist determines the grade of the breast cancer by examining the tissues collected during the biopsy under a microscope. To assign the grade, the pathologist compares the appearance and behaviour of the cancer cells to those of normal cells. More specifically, they analyze the level of differentiation of the cells, structural abnormalities, the presence of tumour necrosis and their growth rate. 

Cancer cells have different morphological characteristics than normal cells. A cancer cell that looks like a healthy cell is said to be “well differentiated,” while a cell that looks very different is “poorly differentiated” or “undifferentiated” (it loses the characteristics of the original cell). The less differentiated the cell is, the higher the grade, indicating that the cancer is more likely to grow rapidly.

To assess the growth rate of the cancer cells, Ki-67 expression levels are measured. This protein increases in quantity as the cells divide. Cells containing Ki-67 are stained using an immunohistochemistry technique and the percentage of cells expressing Ki-67 is assessed. The more positive cells there are, the faster the cancer is progressing. 

Disruption of the expression of ER- and PR-hormone receptors and/or the HER2 receptor is often involved in the development of breast cancer. It is important to determine whether these receptors are overexpressed (i.e., present in greater-than-usual amounts) in cancer cells, in order to develop the most adapted treatment plan. Biopsied cancer cells are tested to evaluate the expression of hormone and HER2 receptors.

Estrogen and progesterone interact respectively with the estrogen receptor (ER) and the progesterone receptor (PR). Hormone receptors are proteins located on the surface of cells. Hormones bind to these proteins to stimulate cell growth. When cancer cells have these receptors, hormones can bind to them and help these cells to grow. 

Estrogen receptors (ER) and progesterone receptors (PR) are involved in approximately 80% of breast cancers, where they are present in greater numbers than in normal cells. ER and PR overexpression is associated with a higher cellular proliferation.  

Cancer cells are always analyzed to check the presence (+) or absence (-) of hormone receptors. When cancer cells have estrogen receptors (ER+), progesterone receptors (PR+) or both, the hormone receptors are positive and the cancer is hormone dependent or hormone sensitive.  

Hormone-dependent breast cancers can be treated by hormone therapy, which changes the hormone rate or blocks their action in order to slow the growth and spread of the breast cancer cells.  

What is HER2?

The HER2 gene is responsible for cell proliferation and can undergo genetic amplification, which causes an overexpression in the HER2 protein, a receptor on the surface of cells. This overexpression leads to sustained and uncontrolled cell multiplication and is involved in 25% of breast cancer cases. 

While most breast cancers have at least one of the three primary receptors identified as therapeutic targets—estrogen, progesterone and HER2 protein—triple-negative breast cancer, which represents 10 to 15% of breast cancers, does not possess any.  

In addition to being ineligible for therapies targeting these three receptors, most triple-negative breast cancers are aggressive tumours, which tend to develop and spread rapidly, and resist other conventional treatments.   

The characteristics of basal breast cancer are both similar to and different from triple-negative breast cancer. Although triple-negative breast cancer is often basal, not all basal breast cancers are triple negative, and vice versa.  

If you have triple-negative breast cancer, different treatments, such as chemotherapy, may be suggested to you. Your healthcare team will consider a number of factors to determine the best possible treatment plan for you.   

Several treatments are being studied to improve management of this type of breast cancer.  

• Inflammatory breast cancer (IBC)
• Paget’s disease of the breast
• Diffuse large B-cell lymphoma (non-Hodgkin’s lymphoma type)
• Soft-tissue sarcoma
• Melanoma
• Metaplastic tumours
• Adenoid cystic carcinoma
• Phyllode tumour
• Carcinosarcoma
• Basal breast cancer

Rarer types of breast cancer include inflammatory breast cancer (IBC) and Paget’s disease. Unlike most other breast cancers, which give rise to one or more separate solid tumours, inflammatory breast cancer tends to form “sheets” or “nests.”

The cancer cells then block the lymphatic system locally, causing these specific signs and symptoms of IBC:

• Persistent itching 
• Redness over more than a third of the breast 
• Feeling of increased heat or burning feeling  in a breast
• Enlarged lymph nodes  
• Increased breast volume 
• Nipple retraction (turned inwards) 
• Swelling or hardening of the skin, which may take on the look of an orange peel  

IBC can manifest in different ways, and this type of breast cancer can sometimes cause pain or sensitivity.  

Several of these symptoms can be associated with other more common health issues, like mastitis or an infection which both cause breast inflammation. Because its symptoms can be similar to benign (non-cancerous) conditions, IBC can be more difficult to detect and may be diagnosed later.  

If you notice any of these changes, or if you have any concerns, consult a general practitioner, a gynecologist or a specialized nurse immediately. Do not wait for your next appointment or mammogram. During the consultation, the healthcare professional may perform a clinical breast exam, assess your personal risk of breast cancer or prescribe diagnostic tests if they think it is necessary. 

For more information on IBC, you can read our blog post Inflammatory Breast Cancer: A Rare and Aggressive Cancer.  

The doctor may order a genetic analysis of the tumour, to check for the mutation or overexpression of genes known to be defective in breast cancer.

BRCA1 and BRCA2

The BRCA1 and BRCA2 genes, acronyms for “BReast Cancer,” play a role in the development of certain types of breast cancer. When these tumour-suppressing genes are muted, DNA repair and cell division control are insufficient, increasing the risks of breast cancer. This phenomenon is present in 5 to 10% of breast cancer cases.