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Vol. 04 Issue 4, Late Fall 1999

What Do We Know about Hereditary Breast Cancer?
The Ribbon 

Mary Kay Dabney, MS, CGC
Genetic Counselor and Coordinator, Cancer Genetics Program
The Cancer Center of Beth Israel Medical Center and St. Luke's-Roosevelt Hospital Center, NY, NY

Q. How common is hereditary breast and ovarian cancer?

A. In 1999, more than 180,000 women will be diagnosed with breast cancer and about 27,000 women will be diagnosed with ovarian cancer in the US. Approximately 44,000 women will die due to breast cancer, while 13,500 will die due to ovarian cancer. An estimated five to ten percent of these breast and ovarian cancers are thought to be hereditary or due to an inherited predisposition. A woman with an inherited predisposition has an increased risk to develop both diseases. It is important to remember that most breast and ovarian cancers are not hereditary.

Q. How is a predisposition to develop breast and ovarian cancer inherited?

A. Each cell in our body has twenty-three pairs of chromosomes, for a total of forty-six. One chromosome from each pair comes from our mother and the other comes from our father. Each chromosome is composed of thousands of genes. Our genes carry the instructions for our growth and development and can determine such physical traits as hair, eye, and skin color. They can also determine whether or not we are predisposed to develop cancer. In 1994, the first major breast and ovarian cancer predisposition gene, BRCA1 or "Breast Cancer 1", was isolated on chromosome 17. A year later, the second major breast and ovarian cancer predisposition gene, BRCA2 or "Breast Cancer 2", was isolated on chromosome 13. In their functional form, both genes are thought to act as brakes on cell growth and are called tumor suppressor genes. An inherited change or mutation in either gene can cause the brakes to fail allowing cells to grow in an uncontrolled manner. This uncontrolled cell growth can lead to the development of cancer. Therefore, a woman with an inherited mutation in either BRCA1 or BRCA2 will be more likely to develop breast and/or ovarian cancer. It is important to remember that not every woman with an inherited mutation in either BRCA1 or BRCA2 will develop breast and/or ovarian cancer.

Q. What is the risk of inheriting a mutation in BRCA1 or BRCA2?

A. A mutation in either BRCA1 or BRCA2 is inherited in an autosomal dominant fashion. This means that an individual needs to inherit only one copy of either gene with a mutation to be predisposed to develop cancer. Each child of a BRCA1 or BRCA2 mutation carrier would have a 50%, or one in two, chance of inheriting the mutated gene and a predisposition to develop cancer. Alternatively, each child of a BRCA1 or BRCA2 mutation carrier would have a 50%, or one in two, chance of inheriting the functional or non-mutated gene. It is important to remember that both men and women can inherit and pass on mutations in BRCA1 and BRCA2.

Q. How significant is a family history of breast and/or ovarian cancer in predicting the presence of a mutation in either BRCA1 or BRCA2?

A. Although some individuals found to have a mutation in either BRCA1 or BRCA2 do not have a family history of breast and/or ovarian cancer, most do. About half of families with hereditary breast cancer have mutations in BRCA1, while most of the remaining families have mutations in BRCA2. Most families with histories of hereditary breast and ovarian cancer have mutations in BRCA1, while a smaller, undefined percentage have mutations in BRCA2. An undefined percentage of hereditary breast and/or ovarian cancer families may have mutations in as yet unidentified cancer predisposition genes. Families with mutations in BRCA1 or BRCA2 can have many women from several generations with breast cancer, as well as women with ovarian cancer. Some women may develop both breast and ovarian cancer. Cancers of the colon and prostate have also been seen in families with BRCA1 mutations, while male breast cancer, melanoma, and cancers of the gallbladder, prostate, pancreas, and stomach have been seen in families with BRCA2 mutations.

Q. What should Jewish women know about BRCA1 and BRCA2?

A. Several hundred different mutations have been identified in both BRCA1 and BRCA2. Recent studies have shown that two mutations in BRCA1 (called 185delAG and 5382insC) and one mutation in BRCA2 (called 6174delT) are more common in individuals of Ashkenazi (Eastern or Central European) Jewish ancestry. Scientists estimate that these three mutations account for most of the inherited predisposition to breast and ovarian cancer seen in the Ashkenazi Jewish population. Additionally, these mutations were found in 1/40, or 2.5%, of Ashkenazi Jews unselected for family history. This is far greater than the estimated frequency of all mutations in BRCA1 and BRCA2 in the general population. This phenomenon can most likely be explained by the presence of these mutations in one or many founders of the Ashkenazi Jewish population several generations ago and is referred to as founder effect. For example, the 185delAG mutation in BRCA1 is thought to have occurred about 40 to 50 generations ago and is estimated to be 1500 to 2000 years old. Other ethnic groups also have mutations in BRCA1 and BRCA2 that are more common in their respective populations due to this same phenomenon.

Q. What is cancer genetic counseling?

A. Genetic counseling is an essential component of cancer risk assessment and the genetic testing process and involves:
· A review of medical records
· A detailed discussion of an individual's medical and family histories
· A brief introduction to genetics and cancer
· An assessment of an individual's risk(s) to develop cancer
· An assessment of an individual's risk to carry a mutation in a cancer predisposition gene
· A discussion of the risks, benefits, and limitations of genetic testing
· Recommendations for cancer screening
In order to discuss this information in detail and facilitate an informed decision about genetic testing, a typical cancer genetic counseling session can last up to two hours and additional sessions are sometimes necessary.

Q. Describe the genetic testing process for BRCA1 and BRCA2.

A. Mutations in BRCA1 and BRCA2 can be detected by obtaining a blood sample. Sometimes stored tissue samples can be used. This analysis can take several weeks to complete and cost up to $2400. Any individual of Ashkenazi Jewish ancestry who decides to undergo genetic testing for mutations in BRCA1 or BRCA2 is initially tested for the three common mutations described above. This test generally costs about $400 to $500 and the results are usually ready within three to five weeks. Many medical insurers are now covering the cost of genetic testing for BRCA1 and BRCA2 for men and women at increased risk to carry a mutation in either gene. Several research studies throughout the United States also offer genetic testing for BRCA1 and BRCA2 for no fee.

Q. If an individual is found to have a mutation in BRCA1 or BRCA2, how does this impact his or her risk to develop cancer?

A. The average woman has an estimated lifetime breast cancer risk of 10 to 12% and an estimated lifetime ovarian cancer risk of 1 to 2%. A woman who inherits a mutation in BRCA1 has an estimated lifetime breast cancer risk of up to 85% and an estimated lifetime ovarian cancer risk of up to 60%. A woman found to have a mutation in BRCA1 who already has breast cancer now has an increased risk to develop cancer in her other breast. BRCA1 mutations may also be associated with an increased risk for prostate cancer in men and colon cancer in men and women. A woman who inherits a mutation in BRCA2 also has an estimated lifetime breast cancer risk of up to 85% and an estimated lifetime ovarian cancer risk between 15 and 30%. A woman found to have a mutation in BRCA2 who already has breast cancer may also have an increased risk to develop cancer in her other breast. BRCA2 mutations are also associated with an increased risk for breast cancer in men. It is important to remember that the cancer risks associated with inherited mutations in BRCA1 and BRCA2 are still being studied and recent data has shown that the risks for breast and ovarian cancer may be overestimated in some families.

Q. If a woman is found to have a mutation in BRCA1 or BRCA2, what are her options?

A. Such a woman is advised to participate in a breast cancer screening program that involves monthly breast self-examination, more frequent physical breast examinations by her gynecologist and/or breast surgeon, as well as mammography. Ovarian cancer screening is also recommended and involves a pelvic examination, a specific blood test called CA-125, and a transvaginal ultrasound examination. Prophylactic mastectomy and oophorectomy are also options considered by some women. However, the extent of breast and ovarian cancer risk reduction after prophylactic surgery is not yet fully known. Colon cancer screening is also recommended and involves digital rectal examination, fecal occult blood testing, and sigmoidoscopy and/or colonoscopy. Currently, researchers are also studying chemopreventive agents like tamoxifen, raloxifene, and oral contraceptives and their effectiveness in reducing breast and ovarian cancer risk both in women in the general population and in women with mutations in BRCA1 and BRCA2.

Q. If a man is found to have a mutation in BRCA1 or BRCA2, what are his options?

A. A man found to have a mutation in BRCA1 or BRCA2 is advised to undergo colon cancer screening as described above. Prostate cancer screening is recommended for men found to have mutations in BRCA1 and involves digital rectal examination and a specific blood test called PSA (prostatic specific antigen).


Q. Will I face discrimination by my employer or health and life insurer if I undergo genetic testing?

A. Many individuals considering genetic counseling and genetic testing for BRCA1 and BRCA2 ask this question. Federal legislation in the form of The Health Insurance Portability and Accountability Act of 1996 or HIPAA and legislation in many states address the issue of genetic discrimination by group health insurers. However, discrimination by employers and life insurers is not addressed by HIPAA and different states have different laws addressing these issues. For more information, contact your state government or a health professional in your area providing genetic counseling and genetic testing.

Q. How can I learn more about genetic counseling and genetic testing for BRCA1 and BRCA2?

A. Genetic counseling and genetic testing for BRCA1 and BRCA2 is available at several centers throughout the US and New York. To find a genetic counselor or other health professional in your area with an expertise in cancer genetics, contact the National Cancer Institute at 1-800-4-CANCER or visit the National Society of Genetic Counselors' Resource Link at http://www.nsgc.org/resourcelink.asp

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Posted 2.15.00 by M. Stewart, BCERF Webmaster
Last Update 06.23.00