By Kari Danziger, MS, CGC

Reviewed by Beth Crawford, MS, CGC
Last updated September 12, 2000

By studying patterns of breast and ovarian cancer in families, researchers have learned that mutations in specific genes can predispose women to these types of cancer. In fact, mutations in just two different genes — BRCA1 and BRCA2 — account for the majority of what scientists term hereditary breast and hereditary ovarian cancer cases.

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Sporadic Breast Cancer and Sporadic Ovarian Cancer

Hereditary factors do not appear to play a role in 80 percent of breast cancer cases and 95 percent of ovarian cancer cases.

If we looked at the family medical histories of 100 women who had been diagnosed with breast or ovarian cancer, we would see that as many as 80 of those with breast cancer and 95 of those with ovarian cancer do not have a strong family history of these cancers. Because hereditary factors do not appear to have contributed to these people's cancer risk, they are said to have sporadic breast or ovarian cancer. Although we can learn something about the risk of developing these types of cancer by looking at factors such as age, reproductive history, diet, alcohol intake, and exercise, nothing in these people's family histories puts them at increased risk for developing either breast or ovarian cancer. And no genetic test exists today that can identify individuals who are at increased risk for sporadic breast or ovarian cancer.

Familial Breast Cancer and Familial Ovarian Cancer

In continuing to look at the family histories of those 100 women, we would probably find that 15 to 20 of them had reported some family history of breast cancer. However, the cases would not necessarily have occurred at an unusually early age, nor would they necessarily have been confined to one side of the family or have occurred in successive generations. These people are said to have familial breast cancer. They appear to be somewhat more likely to develop breast cancer than people with no family history of the disease, but less likely than those with an identifiable hereditary syndrome.

Hereditary factors may combine with environmental factors to cause 15 percent to 20 percent of breast cancer cases.

Hereditary Breast Cancer and Hereditary Ovarian Cancer

Hereditary factors clearly and strongly contribute to 5 percent to 10 percent of all breast cancer cases.

If we continued to look at this same group of 100 women, we'd find that a small number of them — between 5 and 10 — have a strong family history of breast and/or ovarian cancer. This type of family history involves multiple closely-related family members on one side of the family from different generations who have developed either breast or ovarian cancer. Additional features that strongly suggest an inherited pattern include early-onset breast cancer (occuring in women younger than 50); cancer in both breasts, and the diagnosis of ovarian cancer in the family. People who develop breast or ovarian cancer and have this type of family background are more likely to have inherited a mutated gene that causes the hereditary breast and ovarian cancer syndrome. These women are much more likely to develop early-onset breast cancer or ovarian cancer. Most cases of inherited breast and ovarian cancer are linked to inherited mutations in either the BRCA1 gene or the BRCA2 gene.

Clues from a woman's family medical history that would suggest the presence of hereditary breast and ovarian cancer include the following:

• Multiple cases of breast and/or ovarian cancer in the family — especially in closely related relatives in more than one generation (for example, having a mother, sister, and maternal aunt with breast and/or ovarian cancer)
• Young age of onset of breast cancer — especially before age 50
• Individual family member(s) diagnosed with both breast and ovarian cancer
• Breast and/or ovarian cancer in Ashkenazi Jewish families
• Family member(s) with cancer occurring in both breasts — especially if one or both cancers were diagnosed before age 50
• Presence of male breast cancer in the family
• Presence of other associated cancers or conditions suggestive of certain hereditary cancer syndromes — for example, ovarian and early-onset colon cancer in a family may indicate the presence of a different inherited cancer syndrome called hereditary nonpolyposis colorectal cancer (HNPCC)

Overall, in looking at many families with different histories of breast and ovarian cancer, researchers believe that BRCA1 mutations may be responsible for approximately 20 percent to 40 percent of hereditary breast cancer, and BRCA2 mutations may be responsible for between 10 percent to 35 percent of hereditary breast cancer. Researchers are still working to determine exactly how many cases of inherited breast and ovarian cancer can be linked to each of these genes, and to identify the other genes that are responsible for the cases that aren't linked to BRCA1 or BRCA2.

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More on the Genetics of Breast and Ovarian Cancer

Other Hereditary Syndromes

Although BRCA1 and BRCA2 are genes most commonly associated with increased breast and ovarian cancer risk, there are also other genes that, when mutated, increase breast cancer risk.

Although mutations in BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancers, a small number of hereditary breast and ovarian cancers are linked to hereditary syndromes that arise from mutations in other genes. For example, hereditary breast cancer is also part of the rare hereditary cancer syndromes Li-Fraumeni syndrome and Cowden syndrome, which are associated with mutations in the p53 gene and the PTEN gene respectively. Likewise, in some families, hereditary ovarian cancer may be associated with mutations that give rise to other syndromes that are distinguished by the patterns of cancer in the family.

References

Couch F.J. and Weber B.L. (1988). Breast Cancer. In Vogelstein B, Kinzler KW (eds), The genetic basis of human cancer. New York: McGraw Hill.

Pharoah P.D. et al. (1997). Family history and the risk of breast cancer: a systematic review and meta-analysis. Int J Cancer. 71(5):800-9.

Colditz G.A. et al. (1993). Family history, age, and risk of breast cancer. Prospective data from the Nurses' Health Study [published erratum appears in JAMA 1993 Oct 6;270(13):1548. JAMA. 270(3):338-43.

Slattery M.L. and Kerber R.A. (1993). A comprehensive evaluation of family history and breast cancer risk. The Utah Population Database. JAMA. 270(13):1563-8.

Couch F.J. et al. (1997). BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med. 336(20):1409-15.

Shattuck-Eidens D. et al. (1997). BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA. 278(15):1242-50.