Genetic Risk Factors for Breast Cancer

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• Genetics Overview
• How do physicians test for BRCA mutations?
• Who should consider genetic testing?
• Preventing breast cancer in BRCA-positive women
• HER2 (or HER2/neu)
• p53 Tumor Suppressor
• Additional Resources and References

Genetics Overview

DNA (deoxyribonucleic acid), a chemical found on cell chromosomes, is responsible for carrying genetic information. Chromosomes are threadlike structures present within the nuclei of cells. DNA’s double helix structure allows the chromosomes to be replicated during cell division. Genes (segments of DNA) contain instructions for controlling when cells should grow, divide, and die. Certain genes called tumor suppressors slow down the process of cell division, causing cells to die.

Changes in DNA can sometimes cause normal cells to become cancerous by de-activating the tumor suppressor genes. Researchers are still investigating how and why some genes mutate but have discovered that inherited DNA changes may cause cancers to occur more frequently in some families. However, most DNA mutations that cause breast cancer are not inherited; they occur during a woman’s life and may be caused by a variety of factors (many still unknown to medical experts). These factors may include exposure to certain chemicals (such as Aldrin, Alachlor, and Acetamide), high dose radiation (from atomic bombs or from certain types of radiation therapy used to treat other cancers), other environmental exposures, diet, and smoking.

BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) are two tumor suppressor genes that, when functioning normally, help repair damage to DNA (a process that also prevents tumor development). In 1994, researchers discovered that women who carry mutations of BRCA1 or BRCA2 are at higher risk of developing both breast and ovarian cancer than women who do not have these genetic mutations. Currently, women with BRCA1 mutations account for 5% of all breast cancer cases.

Dr. Sandhya Pruthi, MD, a Breast Health Specialist at the Mayo Clinic, estimates that 20% of women who carry BRCA1 mutations will develop breast cancer by age forty, 51% by age fifty, and 87% by age sixty.

How do physicians test for BRCA mutations?

To test for BRCA1 or BRCA2 mutations, a small sample of blood is drawn, and the DNA is analyzed for BRCA defects. In addition to being at higher risk for developing breast cancer, women who test positive for BRCA defects are at a 20% to 60% greater risk of developing ovarian cancer. BRCA1 mutations may also lead to a higher lifetime risk of colon or prostate cancer, while BRCA2 mutations may raise lifetime risk of these and possibly other cancers.⁽¹⁾

Presently, there are over 2000 genetic mutations associated with BRCA1 and BRCA2 genes. Women who test positive for BRCA defects will not necessarily develop breast cancer; they are merely at higher risk for the disease. Additionally, not all BRCA mutations carry the same risk of cancer. A new study conducted at Baylor College in Texas reveals that the protein ATM (ataxia telangiectasia) might be linked to breast cancer development in women who test positive for a mutated BRCA1 gene. Click here to learn more about the ATM protein study.

Who should consider genetic testing?

BRCA1 and BRCA2 genetic testing is a controversial topic among health care professionals. At many clinics, only women whose family histories place them at high risk of developing breast or ovarian cancers are eligible for genetic testing. Any woman considering genetic testing should discuss the process with a physician, nurse, or genetic counselor before proceeding with the testing.

Both men and women may inherit and pass on BRCA1 or BRCA2 mutations. According to the Mayo Clinic, families that typically pass on BRCA defects have the following characteristics:

• Breast cancer in two or more close relatives, such as a mother and two sisters
• Early onset of breast cancer in family members, often before age fifty
• History of breast cancer in more than one generation
• Cancer in both breasts in one or more family members
• Frequent occurrence of ovarian cancer
• Eastern and Central European (Ashkenazi) Jewish ancestry, with a family history of breast and/or ovarian cancer (researchers have identified two types of BRCA1 mutations and one BRCA2 mutation that are especially prominent in this group)

Genetic testing raises some complicated questions women should ask themselves before being tested. Genetic counselors can be very helpful.

• Would I want to know that I am at risk of developing a potentially life-threatening disease?
• How will knowing I am at increased risk of breast cancer change me emotionally?
• What can be done if I find out I may develop a potentially life-threatening disease?
• If I test positive for a BRCA mutation (i.e., an increased risk of breast cancer), should my children be tested?
• How will my family react if I test positive for a BRCA mutation?
• How will the female members of my family react if I find out I am at increased risk for breast cancer? Should they consider genetic testing too?
• How will the results of my genetic tests be used by physicians?
• What are the long term effects in terms of insurance coverage if you are found to carry the BRCA mutation?

Click here to learn more about candidates for BRCA gene testing.

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