Abnormal cell growth

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:

Protection mechanisms

  • Proliferation (multiplication)
  • Cell division
  • Tumour suppression
  • DNA repair
  • Apoptosis (programmed cell-death mechanism)
  • Shortening of telomeres (inactive DNA fragments)
  • Senescence (stopped proliferation)
Protection mechanisms

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.

How does cancer affect proliferation?

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.

How does cancer affect cell division?

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.

How does cancer affect tumour suppression?

In cancer cells, tumour suppressors may be inactivated.

Why do cells need to repair their DNA?

DNA contains the codes for the production of all proteins. Sometimes mistakes are inserted into the DNA:

  • During the cell cycle
  • When exposed to cellular stress (from radiation, ultraviolet [UV] radiation, chemicals, etc.)

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.

DNA repair system

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.

How does cancer affect DNA repair?

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.

How does cancer affect apoptosis?

Cancer cells are able to avoid apoptosis. Without this avoidance, they would be constantly subjected to apoptosis since they have many DNA mutations.

Normal cells have a limited number of cell cycles.

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.

How does cancer affect the telomeres?

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.

How does cancer affect senescence?

Cancer cells can avoid senescence by inactivating the genes involved in this mechanism.

DNA mutations: Problematic errors in the genetic code

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:

  • Environmental factors (e.g. radiation, obesity, overconsumption of alcohol, toxic products like cigarettes)
  • An error that occurs when DNA is copied to produce a new cell
  • Genetic transmission

Mutations can:

  • Be silent (do not change the function of the protein)
  • Make an incomplete protein (making it non-functional)
  • Change the protein’s activity (either decreasing or increasing it)

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: 

  • Mutations that increase gene activity and thus promote proliferation
  • Mutations that inhibit a protective gene
Genetic Mutation

Gene amplification

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.

The role of hormone receptors, HER2 and BRCA1/BRCA2 in the development of breast cancer

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 a protein on the cell surface that is activated by growth factors.
  • It belongs to the EGFR receptor family (EGFR/HER1, HER2, HER3, HER4).
  • When a growth factor interacts with one of these receptors, they combine to activate a cellular response.
  • Activation of EGFR receptors induces cell proliferation, growth and mobility (displacement). It can inhibit apoptosis.

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.

  • Sex hormones (estrogen and progesterone) are important in breast development.
  • Their estrogen (ER) and progesterone (PR) receptors are involved in about 83% of breast cancers and are more strongly expressed than in normal cells. Their activity is therefore abnormal.
  • Overexpression of ER and PR is associated with higher cell proliferation. 
  • Breast cancers with high expression of ER and PR are treated with hormone therapy.
  • BRCA1 and BRCA2 are genes that are involved in the development of certain breast cancers.
  • BRCA stands for BReast CAncer
  • These are tumour suppressor genes that produce proteins involved in DNA repair and gene transcription control, among other tasks. They control genes involved in cell growth. When BRCA1 or BRCA2 mutates, DNA repair does not take place properly and cell division is deficient.
  • The accumulation of mutations due to the dysfunction of BRCA1 or 2 increases the risk of breast cancer: Between 5 and 10% are thought to be attributed to this gene dysfunction.
  • Approximately 1 in 500 people carry the mutation. Among them, 50–85% develop breast cancer.
  • PARP inhibitors are promising molecules for treating breast cancer with a BRCA mutation, and studies are underway to ensure their efficacy and safety.

Invasion or infiltration of cancerous cells

Breast cancer “in situ”

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.

Invasive breast cancer

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.

Metastatic cancer

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.”

The location of breast cancer

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).

StructureName of cancerPrevalence
Galactophoric ductsDuctal carcinoma in situ / Infiltrating ductal carcinoma85%
Mammary lobulesLobular carcinoma in situ / Invasive lobular carcinoma14%
OtherLobular carcinoma in situ / Invasive lobular carcinoma1%
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