Breast cancer and heredity
Breast cancer is one of the most common types of cancer in women; 1 in 8 will develop this condition during her life. Men can also develop breast cancer; in 2018, breast cancer was diagnosed in 131 men in the Netherlands. In women, the number of new breast cancer cases last year was well over 17 thousand.
Hereditary predisposition to breast cancer
In the vast majority of breast cancer cases, besides environmental factors and lifestyle, multiple common variations in low-risk genes play a role. One variation usually has a small effect, but the sum of multiple variations can lead to slightly or moderately altered risks of breast cancer.
In 5 to 10% of breast cancer patients, there is a hereditary form of breast cancer. In these individuals, a mutation is present in a ‘high-risk gene’. Such a gene mutation is an inborn and permanent damage in the DNA.
The most important high-risk genes related to breast cancer are BRCA1, BRCA2 and PALB2. These are so-called tumour suppressor genes. Everyone has these genes and, when they function normally (no mutation), they ensure that damaged DNA is repaired or cleared away, so that tumour growth is prevented. Mutations in these genes cause the gene in question to work less well, as a result of which the risk of cancer increases.
Besides mutations in the genes BRCA1, BRCA2 and PALB2, other genes are also known that can considerably increase the risk of breast cancer, such as mutations in the genes ATM, TP53, PTEN and CDH1. There is also a relatively common, specific mutation (c.1100del-C) in the CHEK2 gene that is known to be able to considerably increase the risk of breast cancer.
Women with a BRCA/PALB2 mutation
A woman with a mutation in one of these genes not only has an increased risk of breast cancer, but also of ovarian cancer. A mutation in the BRCA1 or BRCA2 gene gives a breast cancer risk of 60 to 80%. The risk of ovarian cancer is 35 to 45% with a BRCA1 mutation, and 10 to 20% with a BRCA2 mutation. With a PALB2 mutation, women have a risk of 35-60% of breast cancer and possibly a slightly increased risk of ovarian cancer (exact figures are lacking).
Men with a BRCA/PALB2 mutation
The chance that men - without a hereditary predisposition - develop breast cancer is exceptionally low, namely around 0.1%. In men with a BRCA mutation, the risks of breast cancer rise to 3% (BRCA1 mutation) to 7% (BRCA2 mutation). The risk of prostate cancer also increases: up to 15-20% with a BRCA2 mutation. The effect of a PALB2 mutation in men is not known.
Possible indications of hereditary breast cancer
A BRCA1 or BRCA2 mutation occurs in about 1 in 400 people; PALB2 mutations occur less often. If there is not much breast, ovarian or prostate cancer at a young age in the family, the chance of a mutation in these genes is very small. If these conditions do occur frequently at a noticeably young age, that can be an indication of a hereditary cause.
You may be able to recognise a hereditary predisposition if breast and/or ovarian cancer occurs at a noticeably young age in your family. In addition, there are other possible indications:
- Breast cancer before the age of 40 or ovarian cancer before the age of 50;
- Breast and ovarian cancer in three or more first- or second-degree relatives across multiple generations;
- Breast cancer in both breasts before the age of 50;
- A man with breast cancer in the family.
On the website Het zit in de familie you can find a questionnaire and more information about this.
DNA testing for breast cancer
There are various options when it comes to DNA testing for a genetic predisposition to breast cancer.
iGene DNA test Health
With iGene, too, you can have your genetic predisposition to breast cancer mapped, with the DNA test ‘Health’. In the vast majority of cases (90-95%), breast cancer is not caused by a mutation in a high-risk gene such as BRCA1, BRCA2 and PALB2, but other (genetic or non-genetic) factors play a role.
The genetic risk score that iGene presents for breast, ovarian and prostate cancer is based on DNA variants that are associated with breast cancer in so-called low- and medium-high-risk genes. Variations in these genes individually have a less great impact, admittedly; a sum of multiple DNA variations can in some cases also lead to a (considerably) increased risk score.
An important caveat: at iGene, the high-risk genes BRCA1, BRCA2 and PALB2 have no longer been analysed since 2025. The relatively common CHEK2 mutation (c.1100del-C) is mapped.
Do you suspect that there is a hereditary form of breast cancer in your family? In that case it is advisable to plan a conversation with your GP. The GP will make an assessment of whether you are eligible for clinical genetic testing by a clinical geneticist. The clinical geneticist will (given sufficient indication) carry out a complete gene test and guide you appropriately.
In this blog you can read more about the phased-out optional BRCA analysis at iGene.
Clinical genetic testing by a clinical geneticist
In clinical genetic testing by a clinical geneticist, testing is done specifically for the high-risk genes BRCA1, BRCA2 and PALB2. The whole gene is studied for all gene abnormalities currently known (not only individual mutations, but also larger gene changes). At present, about 6,000 mutations in the genes BRCA1 and BRCA2 are known of which we know that they have an impact on the risk of breast cancer and/or ovarian cancer. For the PALB2 gene, there are currently about 400. Some mutations occur relatively often in certain population groups, other mutations are extremely rare.
DNA testing by a clinical geneticist gives, when it comes to BRCA and PALB mutations, a complete and reliable result. It turns out that in about 15% of families in which genetic testing takes place by a clinical geneticist, a mutation is demonstrated.
A clinical geneticist does not carry out research into DNA variations in so-called low- and medium-high-risk genes.
Not everyone simply has access to such a clinical test. If you are considering this, the GP ultimately has to weigh up whether you are eligible for it.
iGene
HEALTH
iGene HEALTH is our most complete DNA test. It gives insight into your genetic predisposition to various conditions, linked to relevant lifestyle advice. You receive information about your sensitivity to commonly used medicines and the pharmacogenetic profile gives a handy overview that you can share with your GP or pharmacist. And finally you receive information about all kinds of personal traits.