Genetic Factors

Both personal and family histories influence a woman's risk of developing breast cancer. A past medical history for breast cancer is associated with about a fivefold increased risk of contralateral breast cancer. Cancer of the uterus and ovary also has been associated with an increased risk of the development of breast cancer.

It has been recognized for some time that a family history of breast cancer is associated rather strongly with a woman's own risk for developing the disease. The percentage of all breast cancers in the population that can be attributed to family history range between 6% and 12%.8 Empirical estimates of the risks associated with particular patterns of family history of breast cancer indicate the following:8

1. Having any first-degree relative with breast cancer increases a woman's risk of breast cancer 1.5- to 3-fold, depending on age.

2. The higher relative risk is associated with breast cancer with onset younger than age 45 years in one or more first-degree relatives.

3. Having multiple first-degree relatives affected has been inconsistently associated with elevated risks.

4. Having a second-degree relative affected increases a woman's risk of developing breast cancer by approximately 50% (relative risk [RR] 1.5).

5. Affected family members on the maternal side and the paternal side contribute similarly to the risk.

In the early 1990s, the BRCA1 gene on the long arm of chromosome 17 (17q21) was identified as abnormal in a large percentage of hereditary breast and ovarian cancer patients.9,10 A second breast cancer gene, called BRCA2, has been mapped to chromosome 13. Both genes are tumor suppressors. A woman with a strong family history of breast or ovarian cancer, or both, who carries a germ-line mutation of BRCA1 faces roughly an 85% lifetime risk of breast cancer and a 60% risk of ovarian cancer.11 Carriers of the BRCA2 mutation have similar risks for breast cancer but much lower risks for ovarian cancer. Jewish people of Eastern European decent

(Ashkenazi Jews) have an unusually high (2.5%) carrier rate of germ-line mutations in BRCA1 and BRCA2 compared with the rest of the U.S. population.

There is a commercially available test for screening that should be done under the guidance of a genetic counselor. Oophorectomy at completion of childbearing is recommended for carriers of BRCA1 and BRCA2 from high-risk families. Bilateral total mastectomy does reduce the risk of breast cancer occurrence; however, both breast and ovarian cancer have been reported in patients who have had prophylactic removal of these organs. In BRCA carriers who do not opt for surgical prophylaxis, mammography every 6 months is recommended and tamoxifen therapy can be considered.

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