Call it the Angelina Jolie Effect: there’s been a rapid rise in the number of women seeking to be screened for breast cancer gene mutations after the actress announced last May that she was a BRCA carrier and had a prophlactic mastectomy to prevent breast cancer.
“We’ve definitely had more women coming in to discuss their family history and whether genetic testing is appropriate after they heard about Angelina Jolie,” said Dr. Huma Rana, a geneticist at the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute. Many, like Jolie, have had striking medical histories of immediate family members dying of breast and ovarian cancers; some, though, have been worried—well frantic—over a distant cousin’s recent diagnosis with the disease.
Besides offering reassurance that they don’t need to be tested, Rana said she sometimes identifies a strong family history of other kinds of cancers—like colorectal—for which genetic testing would be more appropriate.
Complicating matters, a handful of women have come to Dana-Farber with results in hand from genetic testing they ordered themselves online from a company like 23andMe. Despite being ordered last week by the US Food and Drug Administration to halt its marketing campaign, 23andMe still sells testing kits online for $100 that, in addition to assessing other genetic risks, can tell women whether they carry one of three specific mutations for BRCA that can occur in women of Ashkenazi Jewish descent.
“We’ve been able to confirm positive results of these direct-to-consumer tests,” Rana said, “and provide advice on options for reducing breast cancer risk.”
Testing positive for either a BRCA1 or BRCA2 mutation means an increased risk for both breast and ovarian cancer. About 55 to 65 percent of those who inherit a BRCA 1 mutation will go on to develop breast cancer by age 70 compared to 45 percent of those who inherit a BRCA 2 mutation and 12 percent of the general population, according to the National Cancer Institute. Nearly 40 percent of women with a BRCA 1 mutation and 11 to 17 percent of those with a BRCA2 mutation will go on to develop ovarian cancer, compared to slightly more than 1 percent of those without these mutations.
The vast majority of breast cancer occurs in those who don’t have either a BRCA1 or BRCA2 mutation; in fact, the mutations account for only 20 to 25 percent of hereditarybreast cancers. What this means is that women with a strong family history of breast cancer can’t assume that they’re not still at an increased risk even if they test negative for a BRCA mutation.
This was demonstrated in a study published last week in the journal Cancer Epidemiology Biomarkers and Prevention which found that women with BRCA2 cancers in their family who tested negative for the mutation still had more than four times the average risk of developing breast cancer.
Study leader Dr. Gareth Evans, a geneticist at the University of Manchester, said there are many genes that interplay with certain lifestyle factors, such as body weight or alcohol consumption, to increase breast cancer risk. He recommended that women who have immediate relatives (mother, sisters, daughters) who developed breast cancer before age 50 due to a BRCA2 mutation consider getting more frequent mammograms.
Rana said she wouldn’t recommend increased screening based on this finding. “I don’t think this is clear and convincing evidence that those found to have no BRCA mutations need to be screened differently” based solely on their family history.
But researchers are looking closely at about 25 recently identified gene mutations that are known to play a role in breast cancer risk. “The risks associated with some of these genes are not well defined at this point,” Rana said. As a result, oncologists at Dana-Farber tend to order the full array of genetic testing—called the breast cancer gene panel—only in patients who have already been diagnosed with breast cancer. It’s useful to determine their course of treatment or to assess whether their condition is hereditary in order to inform family members.
Insurance often won’t cover the $3,000 test for those who don’t have cancer, Rana said, since doctors aren’t certain how to advise healthy patients who have genetic mutations other than BRCA1 and BRCA2.
“The risks may outweigh the benefits,” Rana said, if women with only slightly higher than average breast cancer risks opt for unnecessary surgery to have their healthy breasts removed.
“It’s an exciting time for genetic screening,” she added, “but we have to weigh these options carefully and take a thoughtful approach to what we’re offering.”