The Connection Between Genetics & the Risk of Breast Cancer

Abida Taher, MD, PhDOctober 29, 2023

Inheritance risk of disease-causing genetic variants and how they affect you.

1 in 8 women in the United States will be diagnosed with breast cancer in her lifetime.

In 2022, an estimated 280,000 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 51,400 new cases of non-invasive breast cancer. There is no way to tell who will get breast cancer and when, but there are risk factors that can be evaluated, and the implications of this risk assessment can decide future steps. About 85% of breast cancers occur in women who have no family history of breast cancer. These cancers are called random or sporadic. In sporadic cancer, the gene mutations that cause the cancer are acquired (occur only in the tumor cells) and are not inherited. The risk for acquiring gene mutations increases with age and is influenced by environmental, lifestyle, or certain medical conditions.

About 5 to 10% of breast cancer cases are hereditary, meaning that they result directly from gene mutations passed on from a parent.

The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 or BRCA2 gene. BRCA stands for BReast CAncer gene. These genes code for proteins that function as tumor suppressor genes that stop the cells in our body from growing and dividing out of control. Both men and women can have mutated BRCA1 or BRCA2 genes. People who inherit certain mutated versions of these genes have an increased risk of developing different types of cancers including predominantly breast cancer and ovarian cancer but also certain types of pancreatic and prostate cancers. There are also several other genes that have also been linked to an increased risk of developing breast cancer.

It is important to know that not every woman who has a BRCA1 or BRCA2 gene mutation will get breast or ovarian cancer, but having a gene mutation puts you at an increased risk for these cancers, which can be described as follows:

About 50 out of 100 women with a BRCA1 or BRCA2 gene mutation will get breast cancer by the time they turn 70 years old, compared to only 7 out of 100 women in the general United States population.
In most studies, the lifetime risk of female breast cancer in BRCA1 carriers is higher than that observed in BRCA2 carriers.
The incidence of breast cancer diagnosed younger than 50 years of age is higher in BRCA1 carriers compared with BRCA2 carriers, but both groups have an increased risk of premenopausal breast cancer.
About 30 out of 100 women with a BRCA1 or BRCA2 gene mutation will get ovarian cancer by the time they turn 70 years old, compared to fewer than 1 out of 100 women in the general U.S. population.
The incidence of ovarian cancer diagnosed younger than 50 years of age is higher in BRCA1 carriers and overall rare in all carriers younger than 40 years old.
The risk of fallopian tube cancer is also substantially elevated.

You may be at increased risk for a BRCA1 or BRCA2 mutation if your family history includes:

Several relatives with breast cancer.
Any relatives with ovarian cancer.
Relatives who got breast cancer before age 50.
A relative with cancer in both breasts.
A relative who had both breast and ovarian cancers.
A male relative with breast cancer.
Ashkenazi Jewish ancestry (Central or Eastern European) and any relative with breast or ovarian cancer.
A relative with a known BRCA gene mutation.

You may have a higher risk for an inherited mutation if you have had:

Triple negative breast cancer
Breast cancer before age 50.
Male breast cancer.
Breast cancer more than once.
Ovarian cancer, fallopian tube cancer, or primary peritoneal (lining of the abdomen) cancer at any age.
Both breast and ovarian cancers.
Breast cancer or ovarian cancer at any age, and you are of Ashkenazi Jewish ancestry (Central or Eastern European).
Breast cancer, and you have a family member with breast or ovarian cancer.

If you do have a BRCA1 or BRCA2 mutation or a mutation in another gene associated with breast cancer risk, there are options that may help reduce your risk and may either possibly prevent or delay the onset of breast cancer or detect cancer at an earlier, more treatable stage. These include increased surveillance for breast, ovarian, and/or other cancers associated with the gene mutation, such as starting cancer screening at an earlier age and more often with multiple modalities, using risk-reducing medications such as hormone therapy (also called chemoprevention), and preventive surgery, such as the removal of one or both breasts or surgical removal of the ovaries.

If your healthcare team decides that your family health history makes you more likely to get breast, ovarian, and other cancers, they may refer you for genetic counseling. The results of genetic testing can sometimes be difficult to interpret and understand in the right context, which is why it’s important to go over them with a professional genetic counselor.

Knowing your potential risk for hereditary breast cancer can help you and your healthcare team make more informed decisions about your health, before the onset of cancer or before a second cancer has had a chance to develop.