Why the genetic-testing revolution left some people behind — and what to do about it

When Mary-Claire King embarked on a painstaking 17-year-long hunt for a gene linked to breast cancer, she had no inkling that its discovery would be saving lives some three decades later.

King, an evolutionary geneticist, was trying to solve the mystery of why breast cancer was common in some families. This was during the 1970s, decades before the first human genome was

sequenced. In the absence of modern tools such as PCR tests, sequencing and mapping genes took a heroic effort. Cancer researchers at the time were mostly studying tumour-causing viruses,

but several individuals having the disease across generations of the same family suggested that considerable danger could lurk in the human genome, too. What is the best time of the month to

treat breast cancer? “The worldwide impact of something like this just never crossed my mind,” says King, who is at the University of Washington in Seattle. “I was absolutely gobsmacked.”

King named the gene _BRCA1_. Since then, it has become clear that mutations in _BRCA1_ are responsible for about 35% of hereditary breast cancers, and that genetic variants of it and a

related gene called _BRCA2_ are also linked to ovarian, prostate and pancreatic cancers. Drugs have been developed that target cancers with these variants, and genetic tests are available to

identify people who are at risk. But looking back on the impact of _BRCA1_’s discovery also highlights how far there still is to go. Too few people have access to genetic tests and, even

when they do, they have few options to reduce their risk of cancer. Researchers must advocate for and study ways to improve access and to expand the cancer-prevention options available to

people who carry _BRCA1_ and _BRCA2_ mutations. Huge leap in breast cancer survival rat _BRCA1_ encodes a protein that is important for repairing damaged DNA. Although King identified the

_BRCA1_ gene and pinpointed its location1 in 1990, the team that first sequenced it in 1994 included researchers at the precision-medicine firm Myriad Genetics in Salt Lake City, Utah2.

Myriad promptly applied for patents on the gene and used this intellectual property to prevent competitors from developing tests for cancer-associated _BRCA1_ mutations. The high price tag

of Myriad’s genetic tests kept them out of many people’s reach, until a landmark US Supreme Court decision in June 2013 found that such gene patents were invalid. Following the court’s

decision, test prices in the United States plummeted from around US$3,800 to $250, as other providers surged into the field. Yet, testing remains limited, despite studies3 finding that

expanding _BRCA1_ and _BRCA2_ testing to all women could be cost-effective, particularly for those screened between the ages of 20 and 35. There are several reasons for this, including

limited health-care access and concerns about privacy. Lack of awareness among primary-care physicians about genetic testing and conflicting guidelines from professional organizations about

who should be tested contribute, too. For now, however, even in places where testing is an option, it is often made available only to those at high risk of carrying a cancer-associated form

of _BRCA1_, including people with a high rate of cancer in their family (see ‘Testing times’). Many who are eligible do not get tested for _BRCA1_ and _BRCA2 _mutations: one US study4 found

that only about 35% of eligible individuals with ovarian cancer and 56% of eligible people with breast cancer had been tested. Other problems limit the tests’ practical benefits, too.

Reports provided to physicians and people with cancer are often unnecessarily complicated, because they list not only mutations known to increase risk, but also any other unusual DNA

sequences in the genes — even if their relevance is unknown. Many tests also provide data on genes unrelated to cancer, launching fresh medical odysseys for people already dealing with a

cancer diagnosis. When King accompanied a friend diagnosed with breast cancer to a clinical appointment, the attending doctor waved off suggestions for _BRCA1_ testing. “The difficulty with

genetic tests,” they said, “is that they simply beget more tests.” This scientist treated her own cancer with viruses she grew in the lab Simplifying tests and equipping medical staff with

the knowledge to interpret the results could improve uptake. People who learn that they carry worrisome _BRCA1_ mutations need better options to either prevent cancer from developing or

intercept it at an early stage. This is particularly crucial for reducing the risk of ovarian cancer and aiding its early detection. Whereas mammograms can detect some breast tumours early,

there is no equivalent test for ovarian cancer, which is often diagnosed at late stages. At present, cancer detection and prevention are typically achieved by careful monitoring or, in some

cases, surgery to remove the breasts and ovaries. “When I see a 25-year-old woman newly found to have a _BRCA1_ mutation, I’m mostly having the same conversations now that I did long ago for

her options for risk reduction,” says Susan Domchek, a breast-cancer specialist at the University of Pennsylvania Perelman School of Medicine in Philadelphia. “We have a lot of work to do.”

To improve on this, researchers must develop better means of detecting cancers early, and learn more about the biology of early tumours and why some will go on to become malignant whereas

others do not. They must also investigate ways to treat people at earlier stages — an effort that will require learning more about early cancers’ biological hallmarks. By contrast, most

treatments are first developed for and tested in people who have advanced disease. By filling the gaps on testing and giving people with harmful mutations better ways to reduce their risk,

_BRCA1_ and _BRCA2_ testing could become a model for how genetic tests for other cancer risk factors should be implemented. Then, King’s crucial discovery will save even more lives.