Heeding genetic red flags for breast-cancer risk
Doctors here say simple test can identify mutation carriersJanuary 13th, 2011
For a woman whose family has a history of breast or ovarian cancer, a simple test can tell whether or not she's at a higher than average risk of developing cancer in her lifetime, based on her heredity, physicians here say.
In the early 1990s, two gene mutations were discovered and isolated by researchers at the Creighton University School of Medicine's Hereditary Cancer Center, in Omaha, Nebraska, that since have been linked to cancer. Women who have one of those two mutations, known as BRCA1 and BRCA2, have a 56 percent to 87 percent higher chance of developing breast cancer, and a 27 percent to 44 percent higher chance of developing ovarian cancer, says Dr. Deborah Martinez, a breast surgeon at Rockwood Clinic's Cancer Treatment Center here.
The Rockwood Breast Health Center, a clinic within the Rockwood Cancer Treatment Center's Spokane Valley location, offers BRCA1 and BRCA2 testing to its patients and those who have been referred there by a primary care physician, Martinez says.
Cancer Care Northwest, of Spokane, typically tests two to three patients a week for the BRCA mutation, says Dr. Joni Nichols, an oncologist and hematologist at the clinic. Nichols says Cancer Care routinely tests both newly diagnosed breast-cancer patients as well as patients diagnosed with breast cancer in the past but who now should be tested based on changes in their family history.
"We also are referred patients (from primary care providers) that have a family history to see if testing is an option or if they have a relative that has tested positive," Nichols says.
Martinez says that while most cancers occur sporadically in individuals, some families may experience more cancer than others, some of which is because of an inherited genetic mutation.
Up to 90 percent of all hereditary cancers are caused by BRCA mutations, she adds.
"There's not enough testing going on right now for those who are at risk, and it's not just women," she says of the mutation.
Women who've tested positive for the mutation have a number of options to lower their risk of developing breast cancer in their lifetime, from preventive surgeries to increased patient surveillance.
How does a woman know if she or her family members should be tested to see if they have the mutation?
Martinez says she tells her patients to look for specific 'red flags' in themselves and their closest family members before they consider being tested, to see if they are a mutation carrier. Those red flags, she says, include instances of breast cancer before the age of 50, ovarian cancer at any age, two separate instances of breast cancer at any age, both breast and ovarian cancer, and two or more breast cancers in the family with one of those diagnoses occurring under the age of 50.
Martinez says families who are of Ashkenazi Jewish ancestry and have had breast or ovarian cancer at any age also should be tested, as that particular ethnicity has a higher incidence of the BRCA mutation.
Patients who should seek testing also include those related to anyone who has tested positive for BRCA1 or BRCA2. Lastly, Martinez says that any person in a family who's also had pancreatic or melanoma cancer in association with any of the previously listed conditions also should seek testing.
Penny Browne, of Nine Mile Falls, Wash., and one of Martinez's patients who tested positive for the mutation, says she decided to be screened because of her family's history of cancer.
Browne says her two sisters both had breast cancer at young agesone at age 28, discovered while she was breast-feeding, and another in both breasts at age 35. Also, both her father's sisters died of breast cancer before they were 35, she says. One of those aunts also was involved in early genetic research at Creighton University when scientists first began linking the BRCA mutations to breast cancer, she says.
Browne says she found out she was a BRCA carrier about a year ago.
"I expected it, and I spoke with my family about it while I was doing the research, and looked at the options and had an idea of where I wanted to go with it," she says.
Browne opted for what's called a bilateral prophylactic mastectomy, in which both breasts were removed and reconstructed even though she hadn't developed cancer yet. She says she chose that preventative measure because she knew that her chances of developing cancer as a BRCA carrier would be drastically reduced after the procedure.
"I knew I would have to go through the same procedure if I had cancer, but this way I did it on my own terms so I had the ability to heal, and in time prevent (getting cancer) so that I can be here and move forward," Browne says.
She says that while she had some doubts about the decision during the early days of her recovery, she's now confident that she made the right choice for herself and her two children.
Browne says that since her experience, she's taken an active role in educating those around her about what she went through and what risk factors other women should look for in themselves and their families.
Martinez says that women who test positive for the BRCA mutation and opt to have a prophylactic mastectomy reduce their risk of developing breast cancer by more than 90 percent.
Since the BRCA mutations also have been linked to ovarian cancer, Browne says she also underwent a hysterectomy, and had her fallopian tubes and ovaries removed through a procedure called a salpingo-oophorectomy.
That procedure reduced Browne's risk of developing ovarian cancer by up to 96 percent, Martinez says. For women who have the BRCA mutation and don't want to go as far as having a bilateral mastectomy, having the ovaries and fallopian tubes removed has been shown to also reduce the risk of breast cancer by up to 68 percent, she says. Such a surgery precludes bearing children in the future.
Because the BRCA mutation is inherited and the gene isn't expressed on the sex chromosomes, Martinez says both men and women can be carriers, and that if one parent is a carrier, their children will have a 50 percent chance of inheriting the mutation.
Men with a BRCA mutation have an about 6 percent higher risk of developing male breast cancer, Martinez says. Males with the BRCA1 mutation also have a 12 percent to 18 percent higher risk of developing prostate cancer.
She says that while there are two different BRCA mutations that are cancer-linked, a carrier will only have either a BRCA1 or BRCA2 mutation, not both.
BRCA mutation carriers make up only 0.1 percent to 0.2 percent of the general population, she says, adding that about 2 percent of breast cancer patients are BRCA carriers, along with about 10 percent of ovarian cancer patients.
The mutation test is done through a blood sample or oral rinse, and then sent to the only lab in the world that tests for the mutation, Myriad Genetics & Laboratories, in Salt Lake City, Martinez says. Most medical insurance companies will cover all or most of the cost of Myriad's test, she says.
Martinez says test results normally are available in about three weeks, after which she'll meet with the patient to discuss the results and, if necessary, options for preventive treatment.
For women who test positive and haven't developed cancer yet, but don't want to go as far as a prophylactic mastectomy or salpingo-oophorectomy like Browne, the least-invasive prevention method is increased surveillance, Martinez says.
Nichols says that younger women who aren't done having children or aren't ready to take the step of having their breasts or ovaries removed yet are likely to choose this option.
Increased surveillance includes monthly self-breast exams beginning as early as age 18, and annual or semiannual clinical breast exams and mammograms beginning as early as age 25, she says. Annual or semiannual vaginal ultrasounds to screen for ovarian cancer also are recommended beginning at age 25.
Martinez says the next level of prevention, called chemoprevention, involves administering a drug called tamoxifen, which has been shown to reduce, by up to 53 percent, the risk of breast cancer in high-risk women. Oral contraceptives also have been shown to reduce the risk of developing ovarian cancer by up to 60 percent, she says.
Preventive surgery, however, is the most effective way to reduce a patient's risk of developing breast or ovarian cancer. Women with the BRCA mutation who've already had breast cancer and opt for this step also drastically reduce their risk of developing a second cancer, Martinez says, adding that 25 percent of women who've had breast cancer and are a BRCA carrier will develop a second, new breast cancer within five years of their original diagnosis.
For women who aren't BRCA1 or BRCA2 carriers and want to lower their risk of developing breast cancer, both Nichols and Martinez agree that exercise and maintaining a healthy weight, especially for postmenopausal women, is an important step. Eating healthy, eliminating or limiting hormone replacement therapies, and reducing alcohol consumption also can reduce the risk of developing breast cancer, Nichols says.
"However, in patients with the mutation, it's not clear that those lifestyle changes are going to have an effect," she says.
Nichols adds that one of the most important things women can do is talk to their primary health-care provider or gynecologist about their family's cancer history.
"We're not seeing them if they don't have cancer yet, so it's important to educate the gynecologists and the primary care providers about it, so they know what to ask of their patients and if they need to be referred" to be tested, she says.