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Looking Beyond the Stars

On may 14, the New York Times published Angelina Jolie’s op-ed in which she disclosed she had undergone a preventive double mastectomy in February. Her mother died at age 56 after battling breast cancer for 10 years.

Many people share similar backgrounds. They’ve had more than one family member diagnosed with the disease. The difference for Jolie is that cancer in her family is passed from one generation to the next in their DNA. Jolie made the decision to have both breasts removed after undergoing genetic testing that revealed she has inherited a deleterious BRCA1 gene mutation that put her at significantly greater risk for breast and ovarian cancer than the general population.

Every person is born with two copies of the BRCA1 gene and the BRCA2 gene, one copy from his or her mother and one copy from his or her father. BRCA1 and BRCA2 (the name BRCA is derived from BReast CAncer susceptibility gene) are vital for cell health. “In normal cells, they help support the stability of the cell’s DNA,” explains Pam Anderson, R.N. and certified breast care nurse with University Health Care System’s Breast Health Center. These genes suppress tumors. They protect against rapid or uncontrolled cell growth and division.

Very rarely, such as in Jolie’s case, these genes have variants that inhibit proper function. Variants in the genes are inherited too. Several specific mutations on the BRCA1 and BRCA2 genes have been linked to greater incidence of cancer in those who have them. Mutations on other genes have also been linked to breast and ovarian cancer, but BRCA gene mutations account for the largest proportion of hereditary breast and ovarian cancers. Both men and women can carry these deleterious gene variants, which can cause cancer in people of either gender. (Not all mutations are harmful, of course, and some may even be helpful. “Everybody probably has some benign variations in some of their genes,” says Mallory Hire, certified genetic counselor with the Georgia Regents University Cancer Center.)

Pierre Paul Broca, a French physician, first systematically described hereditary breast cancer in the 1860s. More than 100 years later, in the early 1990s, Mary-Claire King discovered the BRCA1 gene, despite intense opposition to her mission. Her work, which confirmed Broca’s suspicions that pre-disposition for cancer can be passed from parent to child through genetic material, is depicted in the 2013 movie Decoding Annie Parker. (Helen Hunt plays Mary-Claire King.)

A few years after King’s discovery, Myriad Genetics patented the sequences of the BRCA1 and BRCA2 genes and developed a test for detecting mutations on them. Up until this past June, when the Supreme Court, in response to a lawsuit brought by the ACLU in 2009, declared that naturally occurring genes cannot be patented, Myriad was the only lab performing this specific genetic testing in the United States.

Filial history of multiple cases of breast or ovarian cancer does not necessarily mean a BRCA gene mutation exists. In addition, even if a parent carries a harmful BRCA1 or BRCA2 gene mutation, he or she may pass on the non-mutated copy of the gene to a child. Furthermore, a child who does inherit a harmful BRCA mutation is not sentenced to a 100 percent certainty of developing cancer. The presence of a mutation does, however, elevate the odds from the 12 percent lifetime risk of getting breast cancer faced by the general population up to an 87 percent lifetime risk. The risk for ovarian cancer rises from the 1.4 percent lifetime risk of the general population up to a 62 percent risk among those who have a harmful BRCA mutation.

Understanding the function and purpose of BRCA genes, how they relate to cancer risk, what it means to have a mutation and what the options are if diagnosed with a harmful variant is complicated. Hyped media reports of Hollywood stars and their medical sagas can exacerbate confusion. Since May, genetic counselors have been busy educating women concerned about whether they should have the BRCA genetic test. Anderson says, “The best person to test is the person who has the cancer. If that person has the mutation, then the rest of the family should be tested.”

    Since 70 to 75 percent of breast and ovarian cancer occurs by chance, not every patient needs testing. Familial cancer accounts for another 15 to 20 percent of breast and ovarian cancers and is attributed to a combination of environmental and genetic, but not inherited factors. A person may have one or two relatives diagnosed with the same kind of cancer in the absence of an identifiable hereditary pattern. This person most likely does not carry a BRCA gene mutation.

“Hereditary breast cancer accounts for only 10 percent of breast cancers,” says Anderson. Criteria specified by the National Comprehensive Cancer Network (NCCN) help physicians and genetic counselors determine candidates for genetic testing: A person who contracted cancer before age 50; a person diagnosed with ovarian cancer at any age; a male with breast cancer; a person with cancer in both breasts; a person with repeat breast cancer; a person with breast cancer that is not fed by hormones (called triple negative breast cancer); a person of Ashkenazi Jewish decent.

If a blood relative has tested positive for a BRCA1 or BRCA2 gene mutation, consider testing. Both sons and daughters of a person testing positive should be tested, with one caveat: Anderson says, “You don’t test someone unless he or she is at the age of ability to handle the information and make good decisions about how to act on the information.” A minor child or young adult may need to wait.

In many cases, the family member or members diagnosed with cancer are no longer living. Whether or not they carried a mutated BRCA gene is unknown. A genetic counselor (“Genetic counseling is a specialized, Masters-trained profession,” says Hire.) can help a person in this situation review family history and determine if he or she meets the medical criteria for testing. For a person who meets the criteria establishing the potential of inherited cancer, most insurance companies pay some portion of the approximately $4,000 test.

This testing is not for breast cancer. A positive result is not a
guarantee that a person will ever get cancer.

Genetic counselors also help sort through the emotions associated with receiving results, as well as practical considerations. “It’s a very individual decision about getting the testing and what to do after,” says Hire. While some people desire to not know if they have a gene mutation, others feel empowered by the knowledge. A person may experience guilt that she tested negative when a sibling tested positive or experience anxiety over the chance that she passed the mutation to her child. Preparing for what it will be like to “know” is a central focus of pre-counseling.

Another important consideration is insurance coverage. State and federal laws now prohibit health insurance providers from denying coverage or raising premiums based on genetic testing outcomes. As Hire emphasizes, “This is not testing for breast cancer.” A positive result is not a guarantee that a person will ever get cancer. On the other hand, disability and life insurance providers are not governed by the same laws. They can deny coverage or payout of benefits based on test results. Hire advises her clients to purchase disability and life insurance policies prior to testing, if possible.

Unfortunately, sometimes the results aren’t crystal clear. A person receiving a “negative” result can be confident that he or she has no deleterious mutation of either BRCA gene, but some people may receive a report stating that they have an “uncertain variant.” This means there’s a change on the gene, but that there is not enough data on this particular change to say whether it is harmful or benign. Data continues to be collected on these variants.  A patient may later be informed of whether the particular variant detected in her test increases her cancer risk or not. Until then, it’s a waiting game. The potential anxiety of feeling in limbo is another aspect of testing covered in pre- and post-test genetic counseling.

Positive results pose the most decisions. The report is returned with an estimate of the person’s risk for cancer, which can be as high as 87 percent for breast cancer and 62 percent for ovarian cancer. Beyond informing offspring and siblings, what’s next? Jolie, as the world learned in May, opted for prophylactic surgery. This alternative is available to all women receiving a positive test result. Preventive removal of the breasts reduces the risk of breast cancer up to 90 percent and preventive removal of ovaries and fallopian tubes reduces the risk of ovarian cancer up to 96 percent. “You can’t guarantee that you got every piece of ovarian or breast tissue,” says Hire, explaining why results don’t reach the 100 percent mark.

Prophylactic surgery can be very successful, but it isn’t for everyone, particularly women in their childbearing years, and it isn’t the only treatment protocol. Knowing that they may never get breast or ovarian cancer even with a harmful gene mutation, some patients choose the route of increased surveillance. This is a strategy geared toward early detection. Starting at age 25, a woman gets a clinical breast exam, a mammogram and a breast MRI every six months. Beginning at age 35, she gets a pelvic exam and an ultrasound of her ovaries and undergoes a blood test every six months.
A third approach to managing a positive test result is to begin chemo-prevention. Drugs such as tamoxifen can reduce the chance of breast cancer up to 53 percent. Oral contraceptives may reduce the risk of ovarian cancer up to 60 percent. No matter what course of action a woman chooses to take, insurance companies normally cover any of these preventive measures, as they are more cost effective than treating the disease.

Fair or not, Angelina Jolie’s critics have come out to comment on her decision in response to her genetic test results. It has created misunderstanding as well. Hire says, “I think it has put pressure on some women to go her route.” As soon as the news hit, Anderson’s phone started ringing. She says, “It was positive in that people who are high risk are seeking discussion about the test. The negative is everybody thinks she needs the test.”
Still, by going public with her personal story, Jolie moved people to ask questions and to seek answers. “The relief women have from getting good information is amazing,” says Anderson. An educated public is like a mighty fortress in the battle against breast cancer.
 

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