When Angelina Jolie wrote a 2013 op-ed piece for the New York Times telling of her decision to have her breasts removed to reduce her high risk for cancer, it brought the conversation about preventive mastectomy into the mainstream. That same year, a Supreme Court ruling eliminated patenting of human genes and opened up the field of genetic testing to competition, creating a dramatic drop in cost to test for mutations related to breast cancer. This combination of events, says associate professor of medicine Allison Kurian, ’95, MS ’06, reshaped the entire landscape of breast cancer screening.
“These two things — huge attention to Jolie and a drop in the cost — changed the world very dramatically,” says Kurian, an oncologist and an epidemiologist. The genetic testing that five years ago cost $4,000 and was not covered by insurance is now about $250 and broadly accessible. “Guess who the new bottleneck is?” asks Kurian. “It’s doctors.”
In a set of research studies published this year, Kurian and her colleagues demonstrate that there’s widespread misunderstanding and significant underuse by physicians of genetic testing for breast cancer patients. Some women who want and would benefit from genetic testing still aren’t receiving it because their doctors don’t bring it up. And many of those who do get tested only do so after surgery or never receive genetic counseling — so they may decide to have life-altering surgery without understanding whether they’re actually at high risk of additional breast or ovarian cancers. At a time when scholarly knowledge of cancer genetics increases each day, Kurian says, it’s critical to figure out how to get this information into the hands of the people making decisions about treatment.
It is now possible, Kurian says, to test for mutations on as many as 40 genes associated with breast cancer. “As a result, there has been a complete about-face in the field,” she says. “Our problem is no longer purely getting genetic information. It is, ‘Do [patients] know what to do with all that information? What about the doctors?’”
In one study of more than 2,500 breast cancer patients, Kurian, a self-described geek who loves data and its application to real-world challenges, found that about two-thirds of the women wanted genetic testing, but less than one-third received it — and only about three-quarters of those received genetic counseling. In another study, she found that half of those who had double mastectomies didn’t actually have the mutations that put them at risk for additional cancers. This means doctors and their patients are making decisions about how aggressive to be in surgery without the benefit of full information.
For women at high risk of hereditary breast cancer, preventive surgery can spare them from disease and even save their lives. But it can expose others to significant risks and side effects without conferring a medical benefit. Prophylactic mastectomy, which can involve the complete removal of the breasts, reduces the risk of breast cancer by at least 95 percent in women carrying the well-known BRCA1 or BRCA2 gene mutation, and almost 90 percent in women with a strong family history of breast cancer. But in lower-risk women, it is not a surgery to be undertaken lightly: It can change patients’ breast function and sensation, their body image and their sexual relationships.
Prophylactic oophorectomy, the bilateral removal of the ovaries, significantly decreases the odds of developing breast and ovarian cancer for very high-risk women by reducing the amount of estrogen and progesterone in the body. This surgery can halt or slow breast cancers that rely on these hormones to grow. It also triggers instant menopause and raises the risks of bone thinning and heart disease.
The key question, then, is how to ensure that each patient gets the optimal treatment. This year Kurian and her colleagues also released a large study of the relative risks of 25 genetic mutations that could help personalize prevention and treatments for breast and ovarian cancer. Now the challenge is to distribute this gold mine of information to those who need it, but equally important is that doctors learn how to use the data to best assist and counsel their patients.
“As we are starting to look at more genes and really understand them, it is harder to know what is the right test to order, and how to implement a plan based on the findings,” Kurian says. “We also have to decide: Should anydoctor be able to order this testing, even without expertise to interpret it? Some of the genes are really well-established; others are an alphabet soup, and we don’t know much [about them]. There is a lot of work to be done on how we use this information.”
Kurian is determined to influence how breast cancer patients are tested and treated nationwide. She is collaborating with the National Comprehensive Cancer Network to revise and update its recommendations on genetic testing. Kurian and her colleagues have also developed an online tool, brcatool.stanford.edu, to help individual women make decisions about testing. Next steps include providing doctors with strategies to help their clinical decision-making and improving how patients are triaged to genetic counselors.
“Women have choices when they have the right testing and counseling,” says Kurian. “Nobody should twist your arm to have surgery. Take your time. You can’t take surgery back.”
Who Gets Tested?
Of 2,529 women with a diagnosis of breast cancer
· 1,648 wanted genetic testing
· 713 received it
· 553 talked to a genetic counselor
Who Has Preventive Surgery?
Of 666 women with a diagnosis of breast cancer who received genetic testing
· 7% reported having mutations associated with increased risk of breast cancer
· 9% reported having mutations of unknown significance
· 72% reported having no mutations
· 29% had both breasts removed
What Do Mutations Mean?
Of 25 mutations suspected or known to be associated with breast and ovarian cancers
· 8 were positively associated with breast cancer
· 11 were positively associated with ovarian cancer
· 1 increased the risk of ovarian cancer 40-fold
Melinda Sacks, ’74, is a senior writer at Stanford.
