After Lucy Benton completed her breast cancer treatment 16 years ago, she thought she was done with cancer. Then last year, the 68-year-old Texas woman learned she had cancer again. This time it was in her ovaries, not her breast. Because these were two distinct cancers — rather than a recurrence of the same one — Benton’s oncologist recommended genetic testing.
“She said it could determine my current or future treatments. So I decided right away that I was going to do it,” Benton says. She tested positive for a mutation in the BRCA2 gene. Having the mutation increases a woman’s chance of developing breast cancer from 12 percent, which is the average risk any woman has, to about 45 percent. It increases ovarian cancer risk from less than 2 percent to as much as approximately 17 percent.
Having both breast and ovarian cancer, as Benton did, can be a sign of hereditary breast and ovarian cancer (HBOC) syndrome. HBOC syndrome is a genetic risk for breast, ovarian, and other gene mutations that are passed down from one generation to the next. Genetic testing can reveal whether women, as well as men, carry a gene mutation that increases the risk for these cancers. Knowledge of a gene mutation can help individuals and families optimize cancer prevention and treatment.
Researchers believe that about 5 to 10 percent of breast cancers are hereditary. This means the increased risk for cancer is a result of a flaw in a gene, also known as a mutation, inherited from a parent. If a parent has a gene mutation, each child has a 50 percent chance of inheriting it. Several known mutations can increase risk for breast cancer. Mutations in the BRCA1 and BRCA2 genes are currently the most common cause of HBOC. A number of other less common mutations, such as those found in the ATM, PALB2, and CHEK2 genes, among others, can also increase risk for breast and other cancers.
You have a mutation. Now what?
Many people first heard of the BRCA1 and BRCA2 mutations in 2013, when actress Angelina Jolie discovered she had a BRCA1 mutation. In order to head off a future breast cancer diagnosis, Jolie had a double mastectomy, which involves the removal of both breasts. Doctors tend to offer this option only to women at very high risk. Then in March of this year, she chose to have her ovaries and fallopian tubes removed to decrease her risk of ovarian cancer.
Preventive surgery is not the only option. Some women, especially those who have not yet had children and don’t want to lose their fertility, may choose another direction if they discover they have a genetic mutation. They might opt to be more vigilant about cancer prevention and screening than people with average risk. This could mean more frequent mammograms or breast MRIs in addition to mammograms.
Until recently, there were no known methods of mitigating the risks of more rare mutations linked to breast cancer. In April 2015, the National Comprehensive Cancer Network, a consortium of centers that creates evidence-based recommendations for cancer treatment, released new guidelines advising patients with CHEK2, PALB2, ATM, and other mutations to receive MRIs. The discovery of mutations, such as CDH1, PTEN, and TP53, warrant a discussion with a doctor about the possibility of having a risk-reducing mastectomy.
For people who already have a cancer diagnosis, discovery of a gene mutation can influence decisions about treatment.
“Women who are facing breast cancer might use these genetic test results to make surgical decisions,” says Carolyn Garby, a genetic counselor at Baylor Charles A. Sammons Cancer Center in Dallas. “If they carry either a BRCA1 or BRCA2 mutation, they could have an increased risk for a second primary breast cancer,” she says. “That might push them to more seriously consider a bilateral mastectomy.” People with certain genetic mutations may respond better to particular treatments, such as a class of chemotherapy drugs known as PARP inhibitors.
Besides the health implications, many people worry that a positive test result could get them dropped from their health insurance or prevent them from getting a job. A federal law called the Genetic Information Nondiscrimination Act prohibits health plans and employers from discriminating on the basis of genetic information, including family history or genetic testing.
“There may be less protection with life insurance or disability insurance,” says Robin Bennett, a genetic counselor and co-director of the Genetic Medicine Clinic at the University of Washington Medical Center. In these cases, some states have laws that protect against discrimination, while others do not. “If that’s something you’re interested in, look at those types of policies before having a genetic test.”
Defining significant family history
People who have a significant family history of breast cancer could be candidates for genetic testing to determine if they have inherited an increased risk for breast and other cancers. Women are about 100 times more likely to get breast cancer than men, though men get the disease, too. Risk increases with age. After gender and age, the greatest risk factor for breast cancer is family history.
“A conversation with your primary care physician, your OB-GYN, or a nurse practitioner is a fabulous starting point to assess your need for genetic counseling,” says Garby.
A significant family history doesn’t simply mean that someone related to you has had breast cancer. Most cases of breast cancer are not hereditary. Any of the following circumstances could suggest that a family has HBOC:
One or more women in the family had breast cancer at age 45 or younger.
One or more women had breast cancer before age 50, and one or more other family members had other cancers.
Family members from multiple generations on the same side had breast or ovarian cancer.
A woman in the family has a second breast cancer in the same or the other breast or has both breast and ovarian cancers.
A man in the family has breast cancer.
There is a history of breast or ovarian cancer and pancreatic cancer on the same side of the family.
There is a history of breast and/or ovarian, pancreatic, or male breast cancer in a family of Ashkenazi Jewish ancestry.
Families that fall into one or more of these categories might discuss genetic testing and counseling with their doctor. Or their doctor may refer them to a genetic counselor who is trained to help patients understand genetic testing and provide additional information so they can determine if testing is right for them. Patients can also search for a counselor through the National Society of Genetic Counselors or by contacting the nearest major medical center.
Information gathering
The first thing a genetic counselor will do is take a detailed medical history on the person seeking testing as well as gather information on family members who have had cancer. The father’s side is just as important as the mother’s, as each parent contributes equally to their child’s complete genetic makeup. What’s more, men who have never had cancer can still pass a genetic risk for it to their children.
Genetic counselors might ask patients to complete a questionnaire before their appointment. They need to know the type of cancer of each affected relative, their age at diagnosis, and their current age or age at death. Because aging is the greatest risk factor for cancer, knowing relatives’ ages at the time of their cancer diagnoses is crucial. “A history in which a woman has a paternal aunt and paternal grandmother with breast cancer in their 40s is much more concerning than if they were both in their 60s,” says Bennett.
People often need to contact relatives for some of the information and access medical records and death certificates of deceased relatives. “You’d be surprised at how often the family lore is a little different from the actual facts of what people died from and how old they were,” Bennett says.
Information about relatives who have not had cancer can be useful, too. Perhaps you want genetic counseling because you suspect HBOC on your mother’s side of the family. While your mother has never had cancer, she did have her ovaries removed. “Having the ovaries removed could mask a family history of ovarian cancer. It also reduces the risk of breast cancer. So a genetic predisposition to cancer can be hidden by that,” says Bennett.
All of this information helps genetic counselors determine the best test for you. “It can be very helpful to have family members attend counseling together,” Garby says. “Let the genetic counselor know who you plan to bring and what the expectation is for that visit. For example, do they all want testing or do they just want to hear the information?”
Who gets the test?
Your family’s history might point to a family member other than you as the best candidate for genetic testing. “The individuals that actually provide the most informative genetic testing are those that have a personal diagnosis of cancer themselves,” Garby says.
Given her diagnosis of both breast and ovarian cancer, Benton was first in line in her family to be tested. Now that it is known that Benton carries the BRCA2 mutation, it’s recommended that her siblings and children (both male and female) be tested as well. While those who test negative for the BRCA mutation are considered true negatives, it doesn’t mean that they have zero risk of HBOC, just that they have the same risk as the general population.
In addition, some labs are offering testing on a panel of genes to look for a range of mutations that may be linked to cancer risk.
“These [panels] analyze anywhere from a handful of genes to over 40 genes, all at the same time,” Garby says. “In the human body we have more than 20,000 genes; therefore, there are many other possible candidate genes that may explain the development of cancer.”
If your counselor identifies an affected living family member, you might need to discuss testing with this relative. Sometimes people don’t want to know if they have a mutation they might have passed to their children.
“If you can explain to them that testing is helpful for you and for future generations of the family, it can change their thinking. Parents tend to want to do everything in their power to protect their children and grandchildren,” Garby says.
The results are in
People often need help coping with genetic test results, no matter what they are. Genetic counselors can provide support. Counselors may also provide a letter to help you share this information with affected family members.
“If you test negative, there can be a profound sense of survival guilt that you’ve tested negative for a condition that your sister, nieces, or other relatives may have,” Bennett says. Sometimes people feel less relief than they thought they would. “It can be hard to believe that a bunch of people in your family got these cancers, and your risk is just average,” she says. “You feel like you’re still at high risk.”
Test results may also be inconclusive, which can cause as much anxiety as never having been tested at all. “There are a few gene mutations that we are not sure if they’re important or not,” Bennett says. This doesn’t mean people can’t use that information. A counselor might recommend more frequent screenings. As research continues, your genetic counselor may learn what your particular mutation means.
“We tell patients to contact us every year, and we’ll check to see if any new information is available about that [mutation],” Bennett says.
A positive test result can also cause grief and anxiety. For many people, though, it is a relief to know their risk and that they have options. After Benton tested positive for a mutation, her sister, Karen Daily, decided to get tested and discovered she also has a BRCA2 mutation. “Just because you test positive doesn’t mean you’re going to get it,” Daily says. “It just means that your chances are increased and that there are things that you can do to lower your risk.”
This article originally appeared in Genome.
Comentários