Genetic testing for breast and ovarian cancers: When family history places you at high risk

For genetic reasons, some women face greater odds that they'll one day develop breast or ovarian cancer. Mutations to breast cancer genes BRCA1 and BRCA2 are responsible for this increased risk.

Most women don't have these mutations — in fact, many women don't need to worry about BRCA mutations at all. But if you're one of the women at high risk, genetic testing gives you the opportunity to find out if you do have a mutated gene.

Before deciding to proceed with genetic testing, consider who such testing is for and what the results might mean for you.

How much higher is the risk of cancer for women with a BRCA mutation?

The lifetime chances of developing breast or ovarian cancer for women who have a BRCA mutation are substantially higher than are the rates for the general population. Women in the general population have a lifetime risk of 12 percent for breast cancer and 1.4 percent for ovarian cancer.

Compare that with a woman who has a BRCA mutation. Her chances of developing cancer by age 70 are much higher:

Many factors come into play in risk estimates, including differences in the gene that's involved, the location of the mutation and the woman's ethnic background.

A study of more than 1,000 women of Ashkenazi Jewish descent provides what could be a clearer picture of the breast and ovarian cancer risks for women with BRCA mutations. Researchers identified a lifetime risk of breast cancer in women with BRCA mutations of 20 percent by age 40, 55 percent by age 60 and 80 percent by age 80. The lifetime risk of ovarian cancer was 54 percent for women with BRCA1 mutations and 23 percent for women with BRCA2 mutations. The researchers also reported that physical activity and a healthy weight during adolescence was associated with delayed onset of breast cancer.

Who is at increased risk of having the mutated genes?

Certain factors point to your likelihood of having a BRCA mutation. You might be at increased risk if any of the following apply to you:

• A history of breast cancer in two or more close relatives, such as your mother and sisters.
• Onset of breast cancer before age 50 in family members on either your mother's or your father's side of the family.
• A history of breast cancer in more than one generation.
• A male relative with breast cancer.
• A family member who has both breast and ovarian cancers.
• Breast cancer in both breasts of a family member.
• A frequent occurrence of ovarian cancer within your family.
• A positive BRCA1 or BRCA2 genetic test in a relative.
• Ashkenazi (Eastern European) Jewish ancestry, with or without a family history of breast or ovarian cancer. Researchers have discovered that 2.5 percent of women of Ashkenazi descent carry a BRCA mutation — an occurrence that's about five times greater than that of the general population.

Just because you have a family history of breast cancer doesn't mean it's hereditary, though. In fact, most people with a family history of breast cancer (familial breast cancer risk) haven't inherited a defective gene, such as BRCA1 or BRCA2. Breast cancer becomes so common in women who live into their 80s and beyond that random, noninherited breast tumors may appear in more than one member of a single family.

Breast cancer cases in women break down roughly this way:

• As many as 80 percent of women who develop breast cancer don't have a family history of breast cancer.
• About 15 percent of women who develop breast cancer do have some family history of breast cancer.
• Only five percent of women who develop breast cancer have a hereditary predisposition for cancer, such as a BRCA genetic mutation.

Who should be tested?

"A woman generally will be advised to have genetic counseling if she has two or more first-degree relatives with breast cancer, ovarian cancer or both cancers — especially if the cancer occurred before age 50," says Sandhya Pruthi, M.D., a breast health specialist at Mayo Clinic, Rochester, Minn. First-degree relatives are your parents, sisters, brothers and children.

Blood tests can identify abnormal BRCA1 and BRCA2 genes, but the value of these tests is controversial. Not everyone needs to be tested for BRCA mutations, and negative results aren't a guarantee that you will or will not develop cancer.

Inherited breast cancer makes up only about 5 percent to 10 percent of all breast cancers. This means, for example, that in the United States in 2004, about 10,000 to 20,000 women will be diagnosed with inherited breast cancer. However, of these cases, only a fraction will be linked to BRCA1 and BRCA2 mutations. Because of this, experts believe that only those women whose family histories place them at high risk of hereditary breast or ovarian cancer should consider genetic testing.

Positive test results: What do you do next?

Identification of a BRCA mutation means you're at high risk of breast or ovarian cancer. You and your doctor must next decide on a preventive strategy.

Preventive strategies include:

• Risk avoidance. Risk avoidance involves engaging in behaviors believed to reduce your risk of cancer, such as limiting alcohol consumption, exercising regularly and losing excess weight. These steps are generally recommended for everyone, whatever your risk level.
• Monitoring (surveillance). Surveillance for breast cancer means having clinical breast exams and mammograms at least once a year. Monthly breast self-examination also is a good idea — it will give you a sense of breast familiarity, which can help you detect any changes in your breasts.

  If you have a BRCA mutation, it's recommended that you have more frequent clinical breast exams, such as every six months, and screening mammograms yearly beginning at age 25 to 35. Your doctor may also recommend additional imaging methods, such as ultrasound or magnetic resonance imaging, as a part of your routine surveillance.

  Surveillance for ovarian cancer includes having an annual or semiannual pelvic exam, transvaginal ultrasound imaging and a blood test to measure your cancer antigen 125 levels beginning at age 25 to 35.

Negative test results: Does this mean you're home free?

If a BRCA mutation isn't found during genetic testing, questions may still remain about your risk of breast and ovarian cancers.

For instance, you may have:

• Negative test results
• A family history of breast cancer
• No known relative with a BRCA mutation

Even though the test results were negative, you may still be at high risk of hereditary breast cancer if your family carries a gene mutation that hasn't yet been identified. Your level of risk therefore can't be based on genetic testing alone. Studies of families similar to your own may allow your doctor to estimate your risk of developing breast cancer.

Another possible scenario is that you could have:

• Negative test results
• A family history of breast cancer
• At least one relative known to have a BRCA mutation

The absence of a BRCA mutation means you haven't inherited your family's increased risk. This doesn't mean, however, that your risk of breast cancer is zero. You're at the same risk as the general population.

Many questions, not so many answers

Much remains to be learned about BRCA mutations. So far, more than 2,000 mutations have been identified on the BRCA1 and BRCA2 genes. But not all of these mutations carry the same risk of cancer. The level of risk associated with each BRCA mutation is unknown.

Having an altered BRCA gene doesn't mean you'll definitely get breast or ovarian cancer. Test results can't determine exactly your level of risk, at what age you may develop cancer, how aggressively the disease might progress or how your risk of death from cancer compares with other women's risk.

If you're at high risk of hereditary breast and ovarian cancers, many difficult decisions lie ahead. Further education and research, as well as discussions with your doctor or a genetic counselor, may help make these decisions easier to face in the years to come.