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Have the phone calls already started?

With the announcement on Tuesday that Angelina Jolie had undergone a prophylactic double mastectomy because she carries the BRCA1 gene, the media were buzzing with the story. Other celebrities such as , and, who also carry the BRCA1 gene, came out with their support. Former American Idol judge Kara DioGuardi wrote in about how carrying the BRCA2 gene lead her to have her uterus and ovaries removed and to have a child by a surrogate.

Such a flood of information will, no doubt, have many women asking about their risk for carrying the BRCA genes and calling your office for advice about it.

Are you ready? Do you know the current recommendations?

How do BRCA1 and BRCA2 gene mutations affect a person's risk of cancer?

(Source: )

BRCA1 and BRCA2 are human genes that belong to a class of genes known as tumor suppressors.

Mutations in both genes have been shown to greatly increase a woman's risk for breast and/or ovarian cancer. Harmful BRCA1 mutations also may increase a woman’s risk of developing cervical, uterine, pancreatic, and colon cancer. Harmful BRCA2 mutations may additionally increase the risk of pancreatic cancer, stomach cancer, gallbladder and bile duct cancer, and melanoma

According to estimates of lifetime risk, about 12.0 percent of women (120 out of 1,000) in the general population will develop breast cancer sometime during their lives compared with about 60 percent of women (600 out of 1,000) who have inherited a harmful mutation in BRCA1 or BRCA2. In other words, a woman who has inherited a harmful mutation in BRCA1 or BRCA2 is about five times more likely to develop breast cancer than a woman who does not have such a mutation.

Lifetime risk estimates for ovarian cancer among women in the general population indicate that 1.4 percent (14 out of 1,000) will be diagnosed with ovarian cancer compared with 15 to 40 percent of women (150–400 out of 1,000) who have a harmful BRCA1 or BRCA2 mutation.

Jolie’s mother, actress , died at the age of 56 from . Jolie underwent genetic testing and found that she carried a mutation of BRCA1 gene. Doctors estimated that this increased her risk of getting breast cancer to 87%, and her risk of ovarian cancer to 50%. As the mother of 6 children, she wanted to be proactive and to minimize the risk as much she could.

In an published in the New York Times, Jolie wrote this about why she decided to make her operation public:

What are the recommendations for BRCA testing?

Currently, there are no standard criteria for recommending or referring someone for BRCA1 or BRCA2 mutation testing.

In a family with a history of breast and/or ovarian cancer, it may be most informative to first test a family member who has breast or ovarian cancer. If that person is found to have a harmful BRCA1 or BRCA2 mutation, then other family members can be tested to see if they also have the mutation.

Regardless, women who have a relative with a harmful BRCA1 or BRCA2 mutation and women who appear to be at increased risk of breast and/or ovarian cancer because of their family history should consider genetic counseling to learn more about their potential risks and about BRCA1 and BRCA2 genetic tests.

The likelihood of a harmful mutation in BRCA1 or BRCA2 is increased with certain familial patterns of cancer. These patterns include the following:

For women who are not of Ashkenazi Jewish descent:

• two first-degree relatives (mother, daughter, or sister) diagnosed with breast cancer, one of whom was diagnosed at age 50 or younger;
• three or more first-degree or second-degree (grandmother or aunt) relatives diagnosed with breast cancer regardless of their age at diagnosis;
• a combination of first- and second-degree relatives diagnosed with breast cancer and ovarian cancer (one cancer type per person);
• a first-degree relative with cancer diagnosed in both breasts (bilateral breast cancer);
• a combination of two or more first- or second-degree relatives diagnosed with ovarian cancer regardless of age at diagnosis;
• a first- or second-degree relative diagnosed with both breast and ovarian cancer regardless of age at diagnosis
• breast cancer diagnosed in a male relative.

For women of Ashkenazi Jewish descent:

• any first-degree relative diagnosed with breast or ovarian cancer;
• two second-degree relatives on the same side of the family diagnosed with breast or ovarian cancer.

These family history patterns apply to about 2 percent of adult women in the general population. Women who have none of these family history patterns have a low probability of having a harmful BRCA1 or BRCA2 mutation.

The cost for BRCA1 and BRCA2 mutation testing usually ranges from several hundred to several thousand dollars. Insurance policies vary with regard to whether or not the cost of testing is covered. People who are considering BRCA1 and BRCA2 mutation testing may want to find out about their insurance company’s policies regarding genetic tests.

What do you see as the positives and negatives of this high-profile story?

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