Who is best suited to undergo BRCA Genetic Testing for Cancer Risk?

Issue 22, Winter/Spring 2014

Film star Angelina Jolie’s May 2013 New York Times editorial, in which she disclosed her decision to undergo preventive mastectomy of both breasts because she carries a BRCA1 alteration (mutation), brought media attention to the power of genetic testing for predicting disease risk. BRCA testing was in the spotlight a second time this year when the Supreme Court ruled unanimously that human DNA cannot be patented in its natural form.

All this public attention has raised questions about BRCA, and many people are wondering if testing is right for them.

There are some key concepts to understand when considering genetic testing. BRCA1 and BRCA2 are genes that produce proteins responsible for repairing damage to DNA. Mutations in either gene increase the risk for breast and ovarian cancers predominantly, and for other cancers as well.

Next, although every woman with a BRCA mutation has a higher risk of developing cancers, not everyone with a BRCA alteration will develop cancer. Finally, most breast and ovarian cancers are not due to an inherited factor. In general, only 5-10% of cancers are thought to be due to an inherited alteration in a predisposing gene.

At its best, BRCA testing can be an empowering step that enables individuals to make well-informed decisions about medical management, such as cancer surveillance, chemoprevention (using medications to reduce the risk of developing cancer), and risk-reducing surgeries. However, testing is expensive and is not always informative. Individuals who are more likely to carry a BRCA alteration may be identified based on their personal and family cancer histories and their ethnic ancestry (see Table 1).

Table 1. Individuals for whom BRCA testing is most likely to be positive

Individuals with a family member who carries a BRCA mutation.

Women with any of the following:

  • ovarian, fallopian tube, or peritoneal cancer
  • early onset breast cancer (diagnosed before age 45)
  • breast and ovarian cancer
  • triple negative breast cancer at age 60 or younger
  • breast cancer and close relatives with breast cancer, pancreatic cancer, melanomas, or aggressive prostate cancers.
  • breast cancer from an ethnic group with a high mutation frequency

Men with breast cancer.

Individuals without cancer but with a family history with features above.

Benefits of testing

Ending uncertainty: A mutation can explain a family history and enable individuals to understand their cancer risks.

Intensified monitoring: Breast cancer surveillance with clinical breast exams, mammograms, and breast MRI beginning at age 25 can aid in early detection.

Implementing risk-reduction options: Measures including preventive surgeries (removal of ovaries and fallopian tubes, mastectomy) and medications (tamoxifen, raloxifene, exemestane) can reduce the risk of developing ovarian and breast cancer.

Risks of testing

Cost: Most insurance plans will cover the cost of testing as long as an individual meets certain criteria. Out of pocket costs for BRCA testing, if not covered by insurance, are hundreds to thousands of dollars.

Doctor in lab

False reassurance: The BRCA genes do not account for all families with hereditary breast and ovarian cancer. Individuals from families with striking histories of cancer remain at high risk even if affected family members have tested negative for a BRCA alteration. Newer tests including multiple genes in addition to the BRCA genes are becoming available. In families without a known mutation, negative test results in someone who has not had cancer are not definitive. In these families, it is not clear whether the family cancer history is attributable to a BRCA alteration, a different genetic alteration, or not heritable at all.

Variants of uncertain significance: Results of BRCA testing can be unclear. A small percentage of people will have an alteration in one of the genes, the significance of which cannot yet be clearly determined. Unclear results can cause stress and anxiety.

Familial issues: Testing may reveal that other family members may share an alteration in a gene that confers increased cancer risk. This can affect family dynamics, particularly when there are contradictory views about genetic information.

Emotional well-being: Some people may experience anxiety or depression if they are found to carry a BRCA mutation. People may worry about their future cancer risk or wrestle with feelings of guilt or anger for having passed down an altered gene. Having good emotional support and open familial communication is ideal for maximizing the value of genetic testing.

3 generations of women.

Discrimination: Health insurance and employment are generally well-protected by federal law, but there are some limitations. Life, disability, and longterm care insurance are not protected.

Getting tested

In the end, counseling may be key, and people who are concerned about their personal or family history of cancer should seek evaluation from a center with cancer genetics expertise. A genetic counselor will obtain the family’s history of cancer, evaluate the patterns of cancer and determine what specific genetic testing is indicated.

For some families, this will mean extensive genetic testing of multiple genes in an effort to explain the history. For others, it will mean testing for a specific mutation previously identified in a relative or evaluating one or two of the most likely genes, and for some individuals it will mean no testing at all.

For certain individuals, then, BRCA testing can provide powerful information –information that may have significant implications for reducing their cancer risk.

Huma Q. Rana, MD

Huma Q. Rana, MD
Center for Cancer Genetics and Prevention
Dana Farber Cancer Institute
Instructor of Medicine
Harvard Medical School

Judy E. Garber, MD, MPH

Judy E. Garber, MD, MPH
Director, Center for Cancer Genetics and Prevention
Dana Farber Cancer Institute
Professor of Medicine
Harvard Medical School