Evidence is growing that all women age 30 and older should be tested for the inherited gene mutations that can cause breast and ovarian cancer, according to British researchers.
“We could prevent thousands more ovarian and breast cancers through a population testing strategy, compared to the current practice of testing only high-risk women,” Dr. Ranjit Manchanda, a gynecological oncology specialist at Queen Mary University of London’s Barts Cancer Institute, told Healthline.
Testing all women age 30 and older also would be cost effective, Manchanda and colleagues wrote in a paper that appeared this month in the Journal of the National Cancer Institute.
The researchers used a complicated mathematical model to arrive at their conclusions.
Several cancer experts called the study solid and thought provoking but questioned some of the underlying assumptions.
Current Testing Practices
The most well-known genes linked to breast and ovarian cancer are BRCA1 and BRCA2.
Together, mutations on these two genes account for 5 to 10 percent of all breast cancers and 15 percent of all ovarian cancers.
Currently, medical guidelines recommend restricting testing for BRCA mutations to women who have been diagnosed with breast or ovarian cancer, or who have family members with breast, ovarian, fallopian tube, or peritoneal cancer.
Women who inherit a mutation on either BRCA gene have approximately a 17 to 44 percent chance of developing ovarian cancer and a 69 to 72 percent chance of developing breast cancer over their lifetime.
These women can reduce their cancer risk with specialized drugs, enhanced screening, or prophylactic surgery to remove breasts or reproductive organs.
On the whole, women who do not carry BRCA gene mutations have a 2 percent risk for ovarian cancer and a 12 percent risk for breast cancer over their lifetime.
But the current practice of limiting testing to high-risk women misses many carriers of BRCA mutations, research has shown.
One reason is that more than half of women with BRCA mutations do not have a family history of breast cancer.
Manchanda and colleagues came to two conclusions.
The first is that it would be cost effective and life saving to add four additional genes — RAD51C, RAD51D, BRIP1 and PALB2 — when testing high-risk women for mutations.
Dr. Yuri Fesko, medical director for oncology at Quest Diagnostics, a leading diagnostic laboratory, agreed.
“We are learning very quickly that there are some additional genes that provide significant risk of breast and ovarian cancer beyond the classic BRCA testing,” Fesko told Healthline.
However, physicians order only BRCA testing for many patients, said Fesko, in part because of health insurance plan limits, which are based on current guidelines.
The researchers’ second conclusion is that expanding this broader panel testing to all women age 30 and older, or almost 100 million women in the United States, would be cost effective and life saving.
This conclusion is more controversial.
If that were done, 237,610 additional cases of breast cancer, or about 2 percent of breast cancer cases in the United States, could be prevented over women’s lifetimes. Another 65,221 or roughly 5 percent of ovarian cancer cases could be avoided, the study estimates.
But several experts questioned some of the researchers’ assumptions.
First, the researchers assumed that 1 in 147 women in the general population carries a BRCA mutation.
“That is far higher than most studies assume,” Elisa Long, PhD, assistant professor at the University of California Los Angeles (UCLA) Anderson School of Management, told Healthline.
Long co-authored a 2015 study that concluded general population testing for BRCA mutations was not cost effective.
“The estimates that I’ve seen for BRCA mutations [in the general population] are more like 1 in 400, 1 in 600 or 1 in 800,” said Long. “It’s like looking for a needle in a haystack.”
The researchers also assumed that a gene test would cost $330 in the United States.
But there is a wide range in the costs of such tests.
Direct-to-consumer testing for BRCA mutations offered by Color Genomics, for example, costs only a few hundred dollars. But testing by major laboratories that physicians typically use, such as Quest, costs much more.
“The billed amount can run into the thousands of dollars,” said Dr. Leif W. Ellisen, program director for breast medical oncology at Massachusetts General Hospital.
The researchers said that if the test cost equaled or exceeded $772, testing all women for mutations would no longer be cost effective.
Ambiguous Gene Mutations
Gene testing can turn up mutations that scientists cannot yet classify as harmful or benign, so-called variants of unknown significance.
That happens 1 to 2 percent of the time for each breast and ovarian cancer gene tested, said Ellisen. That would rise to as much as 12 percent if 6 genes were tested.
“It is well documented in the [research] literature that many patients who have variants of unknown significance in this day and age are getting inappropriate and unnecessary treatment,” including surgery,” said Ellisen.
And, if testing for breast and ovarian cancer gene mutations were offered to all women, ambiguous results could far exceed harmful mutation results, added Ellisen.
Manchanda agreed that ambiguous test results are a serious problem.
“We need to do further research on how to monitor and counsel for variants of unknown significance,” Manchanda said.
The U.S. Preventive Services Task Force, an influential independent, government selected panel of experts, is in the early stages of updating its 2013 recommendation that BRCA testing be limited to high-risk women. The task force weighs harms and benefits but does not consider cost effectiveness.
“There is a lot of interest in what population would benefit most from this testing,” Dr. Alex Krist, a task force member and an associate professor of family medicine and population health at Virginia Commonwealth University, told Healthline. “So, it is fair to say that this is an area that we will be looking closely at.”
Many cancer experts, including Manchanda, doubt the task force will recommend expanding testing to all women without more research on the benefits and harms.
But it is possible that the task force might recommend testing in all Ashkenazi Jewish women, a group at particular risk for harmful BRCA mutations, said Ellisen.
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