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Breast cancer is characterized by abnormal and uncontrollable cell growth. This cell proliferation causes tumour formation and organ dysfunction.
Cells have several mechanisms to protect themselves and prevent cancer from developing. However, cancer cells are able to transform and bypass or inactivate these mechanisms, which are summarized below:
Normal cells don’t proliferate much. They multiply to replace dead cells or repair injuries. Cell proliferation is a process that must be strictly controlled to ensure that the number of cells remains constant.
Cancer cells are uncontrollable because they are able to proliferate autonomously, regardless of the signals the body sends them. They bypass the body’s proliferation-control mechanisms by overproducing growth factors or growth-factor receptors or by activating certain proteins involved in proliferation.
To proliferate, a cell triggers a process called cell division to produce a copy of itself. After this cell cycle, the cell either rests or starts another cycle if it receives more proliferation signals. Throughout the cell cycle, there are several control points that ensure that the developing cell is functional and viable. This supervision is crucial to eliminate dysfunctional cells.
Cancer cells can inactivate control points by massively producing proliferation signals and inactivating control point genes.
Tumour suppressor genes protect cells from excessive proliferation. Tumour suppressors inhibit oncogenic mechanisms (i.e., that promote tumour formation) or activate proliferation-inhibiting mechanisms.
In cancer cells, tumour suppressors may be inactivated.
DNA contains the codes for the production of all proteins. Sometimes mistakes are inserted into the DNA:
These errors can be significant, especially if the erroneous gene is involved in cell survival or proliferation. An error could therefore lead to cancer formation if it is not corrected.
Cells have well-developed mechanism to identify and repair any errors in the DNA. When a mutation is detected, a major tumour suppressor called “p53” activates cell cycle control points to allow DNA repair. Once the error is corrected, the cell cycle continues normally. If the damage is too severe to repair, p53 triggers the programmed cell-death mechanism, called apoptosis, to eliminate any potentially defective cells.
The mechanisms for repairing errors can be defective in cancer cells. Because they proliferate rapidly, many mutations can enter the DNA and increase tumour progression when they occur in a key gene.
When a cell is defective, a programmed cell death mechanism (called apoptosis) is triggered.
Apoptosis is involved in many processes, including organ development and immune response. It is also crucial to preventing the proliferation of cancer cells.
When apoptosis is triggered, the cell is fragmented and dispersed into small bags, which are captured and destroyed by cells involved in the immune system.
Cancer cells are able to avoid apoptosis. Without this avoidance, they would be constantly subjected to apoptosis since they have many DNA mutations.
When the DNA is copied during cell multiplication, the cell is unable to synthesize the terminal portions of its genetic material. The ends of chromosomes are made up of repeated sequences of DNA that do not contain genetic information and are called telomeres. With each cell division, the telomeres shorten. When they become too short, the cell can no longer multiply, so it goes into senescence (stops proliferation) or triggers apoptosis.
Some cancer cells have overcome this limit by over-expressing telomerase, a protein capable of lengthening telomeres. In normal cells, only stem cells express this protein, since they have the ability to regenerate indefinitely to repair tissue.
In a normal cell, when an abnormality is detected (activation of oncogenes or DNA mutations), the cell goes into senescence, a protective mechanism characterized by a permanent cessation of proliferation. The cell is alive, but no longer divides.
Cancer cells can avoid senescence by inactivating the genes involved in this mechanism.
In general, it is DNA mutations that make cancer cells defective. A mutation is a change in the DNA sequence. It can be caused by:
Many mutations are harmless or have benign consequences. They become problematic when they occur in genes that are essential for cell proliferation or survival and are not corrected. These mutations are problematic and turn cells cancerous:
Another type of change is gene amplification, which is a gene that copies itself multiple times. In this scenario, the encoded protein is produced in greater quantity and therefore its effect is multiplied. This is called protein overexpression.
Several proteins are known to be involved in breast cancer, including ER- and PR-hormone receptors, HER2 and BRCA1/BRAC2. They are described below.
HER2 is involved in about 25% of breast cancers. The HER2 gene undergoes gene amplification, which causes HER2 overexpression.
As HER2 controls cell proliferation, its overexpression leads to uncontrolled and sustained multiplication.
Tumours with high HER2 expression are treated with Trastuzumab, an antibody that binds to HER2 and deactivates it. Since its approval, Trastuzumab has significantly improved survival in women with this type of cancer.
A cancerous tumour can remain localized in the mammary gland, without cancer cells infiltrating other organs in the body. This non-invasive breast cancer is called “in situ” (which means “stays in place”). It is the most common type of breast cancer in women. At this stage, the cancer is usually curable.
Sometimes the cancerous tumour can break the lining of the original tissue, making the breast cancer invasive (or, “infiltrating”). The cancer cells leave their original tissue and relocate around the milk ducts. They can migrate into the lymph nodes through blood vessels or lymph ducts. Many invasive cancers can still be treated and disappear completely.
Cells from infiltrating cancers can also migrate to attach themselves to other organs, usually the bones, lungs or liver. They spread outside the breast and form new masses, called metastases. These new tumours are not new forms of cancer, but the same breast cancer that is developing in other parts of the body. This form of cancer is called “metastatic.”
Cancer can develop in different structures of the breast, mainly the galactophoric ducts (the small ducts carrying milk) or lobules (the small structural units that make up the breast).