BRCA Mutations: New Recommendations

Many people are aware that actress Angelina Jolie underwent a double mastectomy to prevent breast cancer, but far fewer understand the genetic mutation behind her decision.

Genetic testing for breast and ovarian cancer risk is an option for certain women, but just knowing about the option of genetic testing has left many women, who have no symptoms of these diseases, wondering how it fits in with mammograms and other forms of breast cancer screening.

My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer, although the risk is different in the case of each woman.

The United States Preventative Services Task Force (USPSTF) recently updated their guidelines on breast cancer screening, and they confirm that screening isn’t appropriate for everyone and should be only be done following careful consideration and thorough counseling.

The USPSTF is an independent panel of experts composed of primary care providers. It reviews scientific evidence and develops recommendations for primary care clinicians and health systems regarding the best ways to prevent and treat disease. The BRCA screening guidelines are part of this work.

The idea behind genetic screening is to definitively assess and reduce the risk of cancer in women with potentially harmful mutations by implementing medical interventions when they show the BRCA1 (Ms. Jolie's form) or BRCA2 mutations that so often lead to cancer.

“My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer, although the risk is different in the case of each woman,” the actress wrote in her opinion piece in the New York Times.

The BRCA1 and BRCA2 genes produce proteins that suppress the formation of tumors, helping to prevent abnormal growths. When mutations to either of these genes cause them to malfunction, cell DNA may not be repaired properly and the unchecked growth of cancer cells may develop.

There are inherited mutations of these two genes that are known to lead to an increased risk of some cancers. BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and around 15 percent of ovarian cancers overall.

The cancers that are associated with these mutations usually occur at younger ages than the cancers that are considered sporadic (occurring without a known genetic predisposition or family history).

In the general population, 12.3% of women will develop breast cancer during their lifetime and 1.4% will develop ovarian cancer. With a known BRCA mutation, a woman’s risk for breast cancer increases to 45%-65% by age 70.

Mutations in BRCA 1 increase ovarian cancer risk to 39% by age 70 and BRCA 2 mutations increase ovarian cancer risk to 10-17% by age 70. The combined prevalence of BRCA 1 and BRCA 2 mutations is also much higher in Ashkenazi Jewish women.

The BRCA1 or 2 gene mutations can be inherited from either a mother or a father. When either parent carries the abnormal gene, a child has a 50% chance of inheriting the same mutation.

Men and women who inherit harmful BRCA1 or BRCA2 mutations, whether or not they develop cancer themselves, may pass the mutations on to their sons and daughter. If a person learns that he or she has inherited a harmful BRCA1 or BRCA2 mutation, this will mean that each of his or her siblings has a 50% chance of having inherited the mutation as well.

The USPSTF recommends that women with a family history of breast, ovarian, tubal, or peritoneal cancer first be screened by their primary care providers to pinpoint aspects of family history that may be associated with an increased risk for BRCA1 or BRCA2 mutations.

The BRCA1 and BRCA2 genes produce proteins that suppress the formation of tumors, helping to prevent abnormal growths.

Family history factors associated with increased likelihood of these potentially harmful gene mutations include: breast cancer diagnosis before age 50, bilateral breast cancer, a family history of breast and ovarian cancer, the presence of breast cancer in more than one male family member, multiple cases of breast cancer in the family, more than one family member with two primary types of BRCA-related cancer, and Ashkenazi Jewish ethnicity.

Women with histories that meet the USPSTF guidelines should be screened when they reach age 18, and should be re-screened at least every five to ten years, as family health histories may change over time.

In order to gather accurate information, the screening tools are standardized questionnaires that explore a family’s health history and include questions such as:

• Did any of your first-degree relatives have breast or ovarian cancer?
• Did any of your relatives have bilateral breast cancer?
• Did any man in your family have breast cancer?
• Did any women in your family have breast and ovarian cancer?
• Did any women in your family develop breast cancer before age 50?
• Do you have two or more relatives with breast and/or ovarian cancer?
• Do you have two or more relatives with breast and/or bowel cancer?

If a woman’s family history is suggestive of a BRCA1 or 2 mutation — if any of the answers to these questions are “yes” — her primary care provider should refer her to a genetic counselor for further assessment and discussion of the risks and benefits of genetic testing.

Task Force chair Virginia Moyer, M.D., M.P.H. put it this way: “Too many American women and families are faced with the challenge of dealing with cancer diagnosis and treatment. We have great hope in the science of genomics to improve screening practices and even prevent some cancers. At this point, the evidence shows that most American women will not benefit from genetic counseling or the test for gene mutations in BRCA1and BRCA2.

“For women who have a family history that might be associated with an increased risk for these mutations, we found that some may benefit from in-depth genetic counseling that thoroughly reviews their family history and, if indicated and after weighing the pros and cons of BRCA testing, receiving the test.”

A positive test result cannot tell whether an individual will actually develop cancer or when.

The task force stresses that genetic testing should not be undertaken without referrals for pretest and post-test counseling, as the results can have significant implications for the lives of the patient and her extended family.

A genetic counselor will describe the possible outcomes of the test, potential interventions if the test is positive, and the implications for extended family members. This can help the patient decide whether or not she wants to continue with the process of genetic testing.

Once the test results are received, the patient requires posttest counseling to understand the results. The results may be positive, negative, or ambiguous.

A positive test, such as Angelina Jolie received, indicates that a person has inherited a known harmful mutation in BRCA1 or BRCA2 gene and therefore, has an increased risk of developing certain cancers. A positive test result cannot tell whether an individual will actually develop cancer or when.

Many women (and men) who inherit a harmful BRCA1 or BRCA2 mutation will never develop breast or ovarian cancer. But they can pass it on to their children, and their siblings are at increased risk of also carrying the gene.

A negative test result requires a little more interpretation.

If a person knows that one of her close relatives — first degree: parents, siblings, or children; or second degree: grandparents aunts, uncles, nieces, nephews, half-siblings — has the BRCA1 or 2 mutation, but their own BRCA1 and 2 test is