Hereditary breast cancer

How common is breast cancer?

More than one in ten Swedish women will be diagnosed with breast cancer during their lifetime, which makes breast cancer the most common type of cancer in Swedish women. The majority of women are diagnosed between 60 and 69 years of age. Breast cancer is uncommon in men and about 40 men are diagnosed with breast cancer in Sweden each year.

What causes breast cancer?

About 80 to 85% of all breast cancer is caused by DNA damage, which can occur during DNA replication or be due to environmental factors. DNA damage occurs all the time and most of the time it is repaired. But with age comes an accumulation of DNA damage, and in turn a higher likelihood that a normal cell transforms into a cancer cell. Age is therefore the leading risk factor for cancer.

The remaining 15 to 20% of all breast cancer is explained by hereditary factors. The impact of hereditary factors on the risk of developing breast cancer can range from small to very large. What they have in common is that individuals with a hereditary risk of cancer are born with one high-risk genetic variant or several low-risk DNA variants that are present in all cells. These variants often affect proteins involved in DNA repair or in other ways protect cells from becoming cancer cells. Therefore, the ability to protect cells from becoming cancer cells may be impaired which results in DNA damage. Normal cells in individuals with a hereditary risk of cancer thus have a higher probability of becoming cancer cells.

In families where several women have been diagnosed with breast cancer, or where one woman has been diagnosed at a young age, hereditary cancer can be suspected. Other factors indicating heredity are cases of ovarian, prostate (before 65 years of age), pancreatic or male breast cancer in the same family.

Underlying genetic factors

In some families with a heredity risk for breast cancer it is possible to identify genetic factors, or rather a genetic variant, that is the underlying cause of cancer development. This is called monogenic inheritance. While the most commonly known genes associated with hereditary breast cancer are BRCA1 and BRCA2, there are several others. Some of these genes are also associated with an increased risk of ovarian, prostate, pancreatic and male breast cancer.

Genes associated with a significantly increased risk of breast cancer include BRCA1, BRCA2, and PALB2. Genes associated with a moderately increased risk include ATM, BARD1, CHEK2, RAD51C, and RAD51D. The following genes are associated with other tumor syndromes associated with increased breast cancer risk:  TP53, PTEN, CDH1, STK11, and NF1.

The clinical genetic testing performed by the Swedish healthcare system today includes genes* associated with a moderate to high risk of breast cancer. For women, a pathogenic variant in any of these genes indicates participation in an established screening program consisting of yearly breast exams with the aim of early discovery of a possible breast cancer. For carriers of pathogenic variants in genes associated with a high risk of breast as well as ovarian cancer (BRCA1, BRCA2, and PALB2) the risk can be reduced by prophylactic surgery.

Genetic regions associated with a minimally increased risk of breast cancer

In addition to the pathogenic variants contributing to a high or moderate risk of breast cancer there are almost 200 genetic regions that are associated with a minimally increased risk of breast cancer. On their own, variants in these regions are associated with a minimally increased risk of breast cancer but together they account for approximately 18% of the hereditary risk.

Hereditary breast cancer with an unknown genetic cause

As previously mentioned it is possible to identify underlying genetic factors in about half of the families with heredity risk for breast cancer. Given that the genetic regions associated with a minimally increased risk of breast cancer are not included in clinical genetic testing, a genetic cause can be identified in about 25% of families that meet the criteria for hereditary breast cancer by todays method’s (described under ”Pathogenic genetic variants associated with a moderate to high risk of breast cancer”). As a result, there are families that are determined to have an increased risk for breast cancer based on their family history, but without an identifiable genetic cause.

Healthy females with an increased risk of breast cancer based on family history of are recommended yearly breast exams. In the case of very high hereditary risk, prophylactic surgery is offered. Breast exams are recommended starting five years of age before the family’s earliest breast cancer diagnosis or by age 40, whichever comes first. From 40 years of age, screening typically proceeds according to national breast cancer screening guidelines. The GeneMate® test includes a genetic test and an assessment of your family’s cancer history, either of which can indicate an increased risk of breast cancer. Therefore, it is important that you fill in your family history when ordering the test. We will help you to get in contact with the appropriate care giver if cancer screening is motivated. 

* GeneMate® tests for pathogenic variants in the following genes: BRCA1, BRCA2, PALB2, TP53, PTEN, CDH1, STK11, NF1, CHEK2, ATM, BARD1, RAD51C, and RAD51D. The complete panel is available at




Anna Hellquist, Genetic Counselor at iCellate Medical AB, PhD Cell and Microbiology