Breast cancer

The term “breast cancer” describes a malignant tumour that develops from breast cells. There are different types of breast cancer, depending on which cells in the breast become cancerous. In most cases, breast cancer starts in the cells of the milk-producing glands, or in the cells of the ducts that drain milk to the nipple. Less commonly, breast cancer can develop in the stromal tissues, which include the fatty and fibrous connective tissues of the breast.

Over time, cancer cells can invade nearby healthy breast tissue and make their way out of the breast through blood vessels and lymphatic vessels. If the cancer cells spread to other parts of the body, metastasis occurs.

While it is true that breast cancer mainly affects women, men, too, can very rarely (about 1%) develop the disease.

Regarding the incidence of breast cancer, statistics indicate that 1 in 8 women may develop breast cancer at some point in their lives. This absolute risk should be taken as a starting point, since each woman’s individual risk may be higher or lower, depending on non-controllable factors such as gender, age (most cases are detected in women over 50), family history or reproductive history. It also depends on controllable factors such as weight, physical activity or alcohol consumption.

Breast cancer is always caused by a genetic abnormality (an “error” in the genetic material). Most of the time, 85-90% of the time, these genetic abnormalities occur sporadically, as a result of the natural ageing process. However, the remaining 5-10% are due to a genetic abnormality inherited from the father or mother.

Along with a healthy lifestyle, gynaecological screening is an essential tool for the prevention and early detection of breast cancer. When breast cancer is detected at an early stage, there is a good chance of recovery.

In the case of a family history, it may also be advisable to have a genetic test to determine if there is an increased risk. In case of a positive result, this will help to determine further preventive strategies.

Historically, the first two genes to be associated with familial breast cancer were BRCA1 and BRCA2. We now know that those who inherit mutations in these genes have an increased risk of developing breast cancer and ovarian cancer compared to the general population. For example, the risk of breast cancer is much higher in women who have inherited mutations in BRCA1 or BRCA2. For women with a BRCA1 mutation, the risk of developing breast cancer at age 80 is 72%. This means that out of every 100 women who have this mutation, about 72 can expect to develop breast cancer if they live to age 80. For women with a BRCA2 mutation, the risk is slightly lower, at 69%.

BRCA genes are not the only cancer risk genes. Various studies carried out in recent years have identified other genes associated with an increased risk of breast cancer. These genes include RAD51C, RAD51D, CHEK2, ATM, BRIP1, PALB2, TP53 and CDH1. Recently, the BARD1 gene has also been added as a moderate risk gene for breast cancer. In most cases, the results obtained from the analysis of these genes allow a detailed and informative genetic counselling and a specific recommendation on the clinical procedure.

When family history suggests the presence of a heritable mutation, or if a close relative has a mutation in one of the risk genes, predictive genetic testing can be offered.

Genetic testing for breast cancer is indicated in patients with a family history suggestive of a familial mutation.

Positive result matching the mutation found in the family

If you have tested positive and have been found to have the known familial mutation that is or was responsible for the development of breast cancer in your family, then you have a significantly higher risk of developing the disease in your lifetime than the rest of the population. It does not imply that you have or will develop the disease, but it does imply that you should intensify surveillance and follow preventive guidelines. In addition, there may be an increased risk of cancer for their offspring.

Positive result in a family in which the causal mutation is not known to exist

In the case of a positive result in a patient for whom no family member with the disease has been or can be tested, it can be assumed that the same mutation also caused the disease in family members who developed breast cancer. In other words, this person also has a higher risk of developing cancer.

Negative result in a family with known causal mutation

If you have a negative result, this means that the known familial mutation responsible for the development of breast cancer in the family is not detected in the patient or that there may be a mutation in a gene that has not yet been associated with breast cancer. This means that you do not have an increased risk of developing breast cancer. Therefore, you have the same risk as the general population (approximately 4%) of developing breast cancer in your lifetime.

Negative result in a family with no known causal mutation

If no known mutation has been found in any family member despite there being some people affected by breast cancer, it may be that another gene is responsible for the development of the cancer and/or that the cancers in your family are not due to an inherited predisposition.

Finally, the result of the genetic test may indicate the presence of a genetic variant that doctors do not have enough information about to be able to assess correctly (variant of uncertain (unknown) significance, VUS). In these situations, the benefit to the patient cannot always be defined.

In order to decide whether a genetic test is advisable, it is ideally important to compile a family tree over 3 generations. By analysing this tree, it can be determined whether there is an increased risk of disease for breast and ovarian cancer and a genetic test can be recommended. As a general rule, it is recommended if at least one of the following criteria is met:

• 3 women with breast cancer, regardless of age
• 2 women with breast cancer, one of whom was diagnosed before her 51st birthday
• 1 woman with breast cancer and 1 woman with ovarian cancer
• 1 woman with breast and ovarian cancer
• 2 women with ovarian cancer
• 1 woman with bilateral breast cancer, first breast cancer before 51 years of age
• 1 woman with breast cancer before the age of 36 years
• 1 male with breast cancer and 1 female with breast or ovarian cancer

If you have or have already had cancer, it is advisable to undergo the study when:

• You have ovarian cancer
• You have or have had triple negative breast cancer before the age of 50 (absence of both hormone receptors and the HER2 receptor)
• In case of therapeutic relevance (e.g. use of PARP inhibitors in women with HER2-negative advanced/metastatic breast cancer and BRCA1/2 mutation)

The decision about whether or not to have a genetic test to establish the risk of breast cancer is a personal one and should always be made after genetic counselling. This counselling should try to answer any questions about:

• What it means to do the test
• How the patient may feel while waiting for the results to come back
• What kind of actions can be considered after the results have been obtained

Genetic diagnosis is an essential preventive tool. If a mutation in one of the genes is detected through genetic diagnosis, the risk of developing cancer increases considerably. It is therefore vital that people carrying the mutation undergo different preventive diagnostic methods on a regular basis.

Accurate and regular follow-up is essential to reduce the incidence of cancer and radically reduce the associated mortality.

There are private insurance policies that cover preventive genetic analysis in first-degree relatives of affected persons with a detected familial mutation.
However, there are private insurances that do not cover the costs and are therefore paid by the patient.