Hereditary Breast Ovarian Cancer Syndrome

This content has been reviewed and approved by

William J. Gradishar, MD FACP
Director, Breast Medical Oncology, Professor of Medicine
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine

Hereditary breast ovarian cancer (HBOC) syndrome causes women who carry the genetic mutation for this cancer to be at increased risk for both breast and ovarian cancer. Characteristics of this syndrome include:

• Early age of onset of breast cancer (often before age 50)
• Family history of both breast and ovarian cancer
• An increased chance of bilateral cancers (cancer that develops in both breasts, or both ovaries, independently) or an individual with both history of breast and ovarian cancer
• An autosomal dominant pattern of inheritance (this means you can get it through either the mother's or father's side of the family)
• An increased rate of tumors of certain other organs, such as the prostate

Other factors that increase the chance that a family has the hereditary breast ovarian cancer syndrome include:

• Family history of male breast cancer
• Ashkenazi Jewish ancestry

What are the BRCA1 and BRCA2 genes?

In 1990, studies done in large families with the above characteristics identified the first gene associated with breast cancer. Scientists named this gene breast cancer 1 or BRCA1 (pronounced brak-uh). Mutations in the gene are transmitted in an autosomal dominant pattern in a family. Women with this mutation have a 65 percent risk of breast cancer by age 70 and a 39 percent average cumulative risk of ovarian cancer by that age, as well as a high risk of early onset breast cancer.

But it was clear that not all breast cancer in families were linked to BRCA1. So studies continued.

In 1994, another gene (similar to BRCA1) was discovered and named BRCA2. Mutations in this gene are also transmitted in an autosomal dominant pattern in a family. Both BRCA1 and BRCA2 genes are tumor suppressor genes. They usually have the job of controlling cell growth and cell death. Women with this mutation also have about a 45 percent risk of developing breast cancer by age 70 and about an 11 percent risk of developing ovarian cancer.

Women with the BRCA2 mutation also have about a 28 percent risk of developing breast cancer by age 50 compared with about a 50 percent risk for those with the BRCA1 mutation. 

What is a founder effect?

The majority of people who have a BRCA1 or BRCA2 mutation have a unique mutation. That means it is specific to them and their family. To date, hundreds of unique mutations have been identified in both BRCA1 and BRCA2. But there are a few exceptions. For instance, specific recurring mutations have been found in individuals of Ashkenazi Jewish descent and in people from the Netherlands, Iceland, and Sweden.

Mutations recur in these groups because of a founder effect. Founders are a small group of people who because of geographic or religious isolation have interbred. When a small group of people interbreeds over generations, specific rare mutations can recur and become more common in the population. This is called a founder effect.

The present day Ashkenazi Jewish population arose from a small group of founders. One or more of those founders must have carried specific mutations in the BRCA1 and BRCA2 genes. In particular, there are three mutations (two in BRCA1 and one in BRCA2) that account for the majority of all BRCA mutations seen in persons of Ashkenazi Jewish ancestry.

This information has practical meaning when it comes to genetic testing because some laboratories now offer ethnic-specific mutation panels. Rather than searching through the entire gene every time a person is tested, in some cases labs can instead first look for specific mutations based on a person's ethnic background.

The founder effect is also important in Ashkenazi Jewish individuals because it has led to an increased occurrence of BRCA mutations in this population.

In the general population, it is estimated that 1 in 800 individuals has a mutation in BRCA1 or BRCA2. In contrast, 1 in 40 Ashkenazi individuals has one of the recurring mutations. This increased occurrence is important for assessing the significance of a family history of breast and ovarian cancer in Ashkenazi people versus other people.

Other Risk Factors for Breast Cancer:

Cowden Syndrome 
Li-Fraumeni Syndrome 
Peutz-Jeghers Syndrome