Genetic Testing Misses Half of Women at Risk for Breast Cancer

Nearly half of patients with breast cancer who, on multigene panel testing, are found to have a pathogenic or likely pathogenic variant for breast cancer do not meet current National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, new research shows.

In a cohort of 959 women who were either currently undergoing treatment or had previously been treated for breast cancer, 49.9% met established 2017 NCCN germline genetic testing guidelines, and 50% did not, lead author Peter Beitsch, MD, Dallas Surgical Group–TME/Breast Care Network, Texas, and colleagues report.

Of those patients who met NCCN guidelines for germline testing, 9.39% had either a pathogenic or a likely pathogenic variant; 7.9% of those who did not meet the guidelines also had a pathogenic or likely pathogenic variant. The difference between the two groups was not statistically significant, the investigators add.

“Our results indicate that nearly half of patients with breast cancer with a P/LP [pathogenic/likely pathogenic] variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines,” the investigators observe.

“We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing,” they conclude.

The study was published online December 7 in the Journal of Clinical Oncology.

However, in a related editorial, breast cancer experts argue that widespread testing would detect genetic variants of unknown significance for which there are currently no established clinical courses of action.

Study Details

For their study, Beitsch and colleagues set up a multicenter, prospective registry with the help of 20 community and academic sites, all of which were experienced in cancer genetic testing and counseling.

They focussed on 959 patients who had a history of breast cancer but had not undergone prior single-gene or multigene testing.

“All patients underwent germ line genetic testing with a multicancer panel of 80 genes,” the authors explain.

“Overall, 83 (8.65%) of 959 patients had a P/LP variant,” they write.

The investigators then considered findings from only BRCA1 and BRCA2 genetic testing.

In this subgroup analysis, positive BCRA1/2 rates were fourfold higher among those who met current NCCN germline testing guidelines, at 2.51%, compared to those who did not, at 0.63% (P = .020).

However, the authors point out that patients with a clearly identifiable personal and family history consistent with NCCN testing guidelines were likely to have already undergone genetic testing and therefore would have been excluded from the study.

In contrast, rates of variants of “uncertain significance” were virtually identical between those who met current NCCN guidelines for genetic testing and those who did not.

“Carriers of clinically actionable variants in genes other than BRCA1/2 are likely to fall outside of the current guidelines,” Beitsch and colleagues point out.

“Results of our study suggest that a strategy that simply tests all patients with a personal history of breast cancer would almost double the number of patients identified as having a clinically actionable genetic test result,” they reason.

Variants of Unknown Significance

In a related editorial, Kara Milliron, MS, and Jennifer J. Griggs, MD, MPH, both from the University of Michigan Cancer Center in Ann Arbor, argue that widespread uptake of genetic testing would increase the likelihood of identifying pathogenic variants of genes for which there are no established guidelines for reducing cancer risk.

For example, pathogenic variants in ATM are associated with an increased breast cancer risk, “but there is insufficient evidence to support risk-reducing breast surgery or bilateral salpingo-oophorectomy,” they point out.

Furthermore, more widespread testing is likely to increase detection rates of variants of unknown significance, which were common in the study by Beitsch and colleagues.

“These variants present challenges for both patients and medical providers in the management of ambiguity that arises in a patient with a malignancy and family members,” Milliron and Griggs write. This issue is particularly problematic in certain racial and ethnic groups in which such variants are both more common and more poorly characterized, they add.

Of greater concern are barriers to high-quality counseling following genetic testing.

“The shortage of genetic counselors has been well documented,” the editorialists note, and currently, “many patients receive genetic testing without seeing a genetic counselor,” they state.

Lastly, the cost of widespread testing and counseling cannot be overlooked, especially when considering expanding that testing to all patients with breast cancer.

Medicare does cover BCRA1/2 testing, and some states cover genetic testing.

“Thus, costs to patients may be prohibitive in the most vulnerable populations,” the editorialists write.

NCCN guidelines for genetic testing were published about 20 years ago and were designed to identify patients who were most likely to carry BRCA1/2 variants.

This was done to reduce the number needed to test; at that time, the cost of genetic testing was $2000 to $5000 per test.

Now, it is approximately 10 times less costly to conduct germline testing than it was when the guidelines were originally established.

Still, Milliron and Griggs calculate that the call to have all women with breast cancer undergo genetic testing would amount to about $400 million in total costs to insurance companies. They arrive at this estimate by considering the current cost of $1500 per test multiplied by the number of new breast cancer cases diagnosed each year in the United States.

Genetic Testing in New NSCLC: Worth the Effort?

“If you build it, they will come,” the saying goes, but has that been the case with genetic/genomic testing in patients with newly diagnosed non-small cell lung cancer (NSCLC)? After all, research has shown that about 40% of patients with NSCLC have one of these molecular alterations in their tumor, and using these tests can help sort out those who have KRAS-mutated disease, versus epidermal growth factor receptor (EGFR) mutations, versus ALK, ROS1, or RET translocations, guiding patients to the most effective targeted therapy.

A recent international survey of oncologists revealed that while the use of genetic/genomic is on the rise, many clinicians are either bypassing testing altogether, or if the patient did undergo testing, the results were not used to make treatment decisions.

 Overall, genetic testing can help clinicians get a better handle on the subtype of NSCLC they are contending with, based on specific molecular alterations. This improved disease description will give patients a better chance of receiving the most effective treatment with the least toxicity and, ideally, at the right price point.

For instance, EGFR mutations are currently the most common genomically classified subgroup of NSCLC. These mutations tend to be more prevalent in tumors with adenocarcinoma histology, in patients who have never smoked tobacco, in patients of East Asian race, and women. Results of genetic/genomic testing can then set patients up for treatment with agents such as gefitinib (Iressa) and erlotinib (Tarceva).

Guidelines established by specialty groups, including the College of American Pathologists and the International Association for the Study of Lung Cancer, recommend testing for EGFR mutations (along with testing for ALK mutations) in patients with advanced-stage disease. Whether early-stage patients should undergo the same is uncertain.

“The question of whether or not to test a diagnostic specimen in early-stage disease is a local decision that must be made in conjunction with each institution’s oncology care team, as insufficient published evidence supports a universal recommendation,” according to 2013 guidelines from the groups mentioned above. “The benefits of testing all early-stage disease patients must be balanced against the cost of performing testing that may not be used to select therapy for the patients who never have relapse.”

But genetic screening in early NSCLC isn’t out of the question, wrote Jean-Charles Soria, MD, PhD, of Gustave Roussy Cancer Center in Villejuif, France, in an email to MedPage Today. He pointed out that there is a debate over the risk of relapse in stage I-II cancer, but even if that risk is over a 5-year period, it “reaches 50%, so I also believe it could help.”

 Even in early-stage NSCLC, molecular testing can serve as a decisive factor in the choice of therapeutic strategies for patients, explained Frédérique Nowak, PhD, of the French National Cancer Institute (INCa) in Boulogne-Billancourt, France in an email to MedPage Today.

For example, early testing can rule out if a patient is simply ineligible for treatment with gefitinib, an EGFR tyrosine kinase inhibitor (TKI). Nowak cited a 2012 study that she and Soria co-authored that found that EGFR testing avoided a median of 8 weeks of administration of gefitinib for EGFR-negative patients.

An added benefit to testing? The potential for a significant reduction in treatment costs. “In France in 2010, about 15,000 of the 16,834 patients with lung cancer who benefited from EGFR screening were EGFR-mutation negative and thus were ineligible for TKI-EGFR treatment,” Nowak stated.

“As 8 weeks of gefitinib treatment costs €4,600 per patient in France [about $5,000], this would mean overall savings of €69 million [about $74 million]. According to the numbers of EGFR tests performed in 2011, the spared costs should be even greater,” she added.

Seven years ago, INCa, along with the French Ministry of Health, launched a campaign to implement molecular testing for all cancer patients across the French national healthcare system. The network is made up of 28 regional molecular genetic centers that perform tests for free for all patients in their regions.

 Nowak reported that the network now “is fully deployed in the country. For lung cancer, the tumors of more than 24,000 patients were screened for EGFR mutation and ALK rearrangement in 2014. It roughly corresponds to all non-epidermoid NSCLC patients at a metastatic stage in France.”

Back to the survey results, which revealed that one of the impediments to implementing genetic testing in newly diagnosed patients may be the wait for the results – the turnaround time for test findings can range from 1 to 2 weeks. About a quarter of U.S.-based survey respondents stating that was too long.

In general, lung cancer takes some time to develop before a diagnosis is made; a few extra days of waiting for test results that can have a major impact on treatment course and patient outcomes shouldn’t be that onerous, noted survey leader James Spicer, PhD, MBBS, of King’s College London.

“Personally — and I think this is a fairly common viewpoint — turnaround within 1 week — 5 working days — would definitely be acceptable; 2 weeks or more becomes a problem,” he said.

While Spicer told MedPage Today that he wasn’t surprised by the survey results, his group also did not find any evidence that clinicians were skeptical about EGFR testing overall. Instead, it may be a matter of continual education to emphasize the benefits of genetic testing in NSCLC patients across the board.

“We should be aiming for every suitable NSCLC patient to be tested, and every patient receiving an appropriate treatment for their type of lung cancer,” Spicer said in a written statement about the survey results. He added that “there is still work to be done in emphasizing the importance of obtaining EGFR test results prior to the initiation of treatment, and using this vital information to select optimum therapy.”

Metastatic Prostate Cancer Needs Genetic Testing; Here’s Why

Germline genetic testing should be offered to men with metastatic prostate cancer, regardless of age or family history, say the authors of a new study.

The incidence of germline mutations in genes that mediate the DNA-repair processes in patients with metastatic prostate cancer was found to be significantly higher than that in men with localized disease (11.8% vs 4.6%).

Almost three quarters of these men also had a first-degree relative with cancers other than prostate cancer.

These cancers include breast, ovarian, pancreatic, and other gastrointestinal malignancies, as well as leukemia and lymphoma.

The findings were published online July 6 in the New England Journal of Medicine.

“This information is important, not only for the patient but for other family members as well, as they too may be predisposed to cancer,” said Michael F. Walsh, MD, co-lead author of the study and a geneticist and pediatric oncologist at Memorial Sloan Kettering Cancer Center in New York, New York.

Dr Walsh recommended that family members should also be offered testing, in addition to the patients. “There are preventative and risk reduction options that may be relevant for family members which they should consider if also carrying the same pathogenic germline mutation,” he said.

These findings also can potentially change clinical practice. “We are now at a point where we have specific therapies that we can offer people with heritable DNA repair mutations,” Dr. Walsh told Medscape Medical News.

These include agents such as poly adenosine phosphate ribose polymerase inhibitors, for which there has been a precedent to try these therapies in women with breast and ovarian cancer. “These are emerging therapies and only available in clinical trials at this time,” he said. “And these trials are ongoing now.”

Higher Rates in Metastatic Disease

Previously, as part of other research, the authors sequenced germline DNA exomes from a population of men with metastatic prostate cancer. That is when they unexpectedly found that 8% of these men carried pathogenic germline mutations in DNA-repair genes.
Now, Dr Walsh and colleagues have assessed mutations in 20 DNA-repair genes that are associated with autosomal dominant cancer-predisposition syndromes in 692 men with metastatic prostate cancer.

The objective was to confirm the earlier findings and further ascertain the spectrum and prevalence of these mutations in this population.

They identified a total of 84 germline DNA-repair gene mutations that were presumed to be deleterious in 82 men in the cohort (11.8%).

Mutations were identified in 16 genes; these included BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]).

The frequency of mutations did not seem to be affected by a family history of prostate cancer or the patient’s age at diagnosis.

However, it was significantly more prevalent than the 4.6% frequency observed in the 499 men with localized prostate cancer (P < .001). This included patients with high-risk disease.

A family history was available for 72 of 82 men (88%) with mutations in DNA-repair genes and for 537 of 610 men (88%) without them.

In both groups of men, 22% (16 of 72 men with DNA-repair gene mutations and 117 of 537 men without them) had a first-degree relative with prostate cancer (P = 1.0).

But 51 patients with DNA-repair gene mutations (71%) had a first-degree relative with another cancer type compared with 270 patients (50%) without the mutations (odds ratio, 2.4; P = .001).

The authors point out that the 11.8% overall frequency of germline mutations seen in this study is substantially higher than the 1.2% to 1.8% incidence of BRCA2 mutations detected in localized prostate cancer or the 7.3% incidence of mutations in 22 tumor-suppressor genes identified in familial prostate cancer.

Even though testing for gene mutations is becoming increasingly available, Dr Walsh recommends that patients be tested in a comprehensive cancer center, where they will have access to genetic counselors.

“In addition to coming across mutations in the genes that we know are harmful, variants of uncertain significance may also be detected in these genes,” Dr Walsh said. “So we need to make sure that patients are being counseled appropriately by an experienced team.”

At the current time, it is unknown whether these mutations are prognostic, and that needs to be studied, he added. “This research is ongoing.”

‘Angelina Jolie Effect’: BRCA Testing Doubles

Twice as many women were tested for BRCA1/2 mutations in a North American clinic in the 6 months after the revelation by actress Angelina Jolie that she had undergone a prophylactic mastectomy after finding out that she was a carrier.

Importantly, the increase in genetic testing was appropriate, as the proportion of women found to be carriers remained constant, the researchers note.

The finding illustrates “the profound impact that prominent figures like Jolie can have on public awareness of health issues,” commented lead author Jacques Raphael, MD, clinical fellow at Sunnybrook Odette Cancer Center in Toronto.

He was speaking at a presscast held by the American Society of Clinical Oncology ahead of the 2014 Breast Cancer Symposium in San Francisco, where the study will be presented.

Increase in Testing, But Still Appropriate

BRCA1/2 mutations dramatically increase the risk for breast and ovarian cancer. The mutations are rare, found in about 2% to 4% of women, but are more likely to be found in those with a family history of breast and ovarian cancer and those with personal risk factors, such as Ashkenazi Jewish descent.

Jolie’s announcement, in an article entitled My Medical Choice published on May 14, 2013 in the New York Times, was extensively reported across all media, and at the time, several breast cancer experts predicted that the huge publicity would lead to an upsurge in genetic testing for BRCA1/2 mutations.

“People in the community who see high-risk breast cancer have been very aware of what has been dubbed the ‘Angelina Jolie effect,’ this phenomenon of more women and their families seeking out genetic testing,” commented Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston, who moderated the presscast.

What is interesting about this study, he said, is not just that the authors were able to document the increase in genetic testing, but they also show that it is “the right people that should be seeking out genetic testing.”

It’s a real triumph for what a public disclosure of a health problem can accomplish.

“The key point is that the same percentage of patients actually had the genetic mutation, and the same proportion met the criteria for testing” in the periods before and after the news, he said. “These were not inappropriate people who had somehow been frightened or alarmed by the messages that came forward; rather, because of their clinicians’ or their own awareness, these were perfectly appropriate individuals who should be getting genetic counseling who were seeking that genetic counseling…. It’s a real triumph for what a public disclosure of a health problem can accomplish for patients and society.”

In their study, Dr. Raphael and colleagues documented the upsurge in genetic testing seen in their Toronto clinic. Referrals to the clinic rose from 418 in the 6 months before to 916 in the 6 months after the announcement (referrals increased by 90%).

Of these referrals, 213 individuals (44%) qualified for genetic testing before, compared with 437 (48%) after (genetic testing increased by 105%).

This genetic testing found 29 carriers of BRCA1/2 mutations (6%) among the patients who were referred before, compared with 61 carriers (7%) among those who were referred after the announcement (the number of carriers found increased by 110%).

The fact that the proportion of carriers among those tested remained constant showed that the genetic testing was appropriate, both Dr. Raphael and Dr. Burstein emphasized.

When comparing the women who were tested before and after the announcement, Dr. Raphael noted that there was little difference in the median age (50 and 51 years old, respectively) or in the proportion of women who had already had breast cancer prior to testing (26% before, 30% after the announcement). Also, there were similar proportions of individuals who had a history of breast and ovarian cancer in the family, a history of male breast cancer in the family, or who had breast cancer diagnosed at or before age 35.

There was a slight increase in the number of men who came for testing (10% of those tested before vs 13% of those tested after the announcement).

The figures show clearly that there was an increase in referrals after the announcement, Dr. Raphael said, “but what is interesting is that the quality of referrals remained the same, meaning that appropriate and high-risk referrals were being made to the clinic.”

These referrals were well justified, and were not just the result of increased media publicity about the testing. They all met the criterion for testing that has been laid down by the Ontario Ministry for Health, he said.

Dr. Raphael noted that the study is now continuing to see if the increased demand for genetic testing forBRCA1/2 mutations is continuing or if the effect is tailing off after the initial 6 months. If it continues, there will be a challenge to meet the increased demand, both in terms of time and costs, for screening, counseling, testing, and preventive surgery, he said.

“After Angelina Jolie’s story, the current model of genetic counseling may need to be revised,” the authors suggest.

In Canada, referral costs around $300 and the genetic testing around $1000, Dr. Raphael noted. For the clinic, referral costs went from $146,000 to $275,000 and the genetic testing costs went from $213,000 to $437,000 during the 6-month periods before and after the announcement, he said.

“What is fascinating about the Angelina Jolie effect is how powerfully it prompted women to seek genetic counseling for breast cancer, particularly those women who were most in need of it,” commented Dr. Burstein.

“In this instance, Jolie’s choice to share her story really made clinician and patients aware of the importance of genetic testing in a way that they were not before, and helped drive patients into action,” Dr. Burstein said in a statement.


Gene-testing company ‘here to stay’

The $99 personal DNA test was designed to detect a range of gene variants
Personal-genetics company 23andMe says it is “not going anywhere”, after the Food and Drug Administration ordered it to stop marketing-spit testing kits.

“Our mission is unchanged,” it says.

On Friday, the Californian company stopped giving its health-risk results – based on gene variants – to those who had bought the tests after 22 November.

The FDA feared they would make poor decisions, such as opting for unnecessary surgery on the basis of a risk for a gene linked to cancer.

Founded in 2006 by Linda Avey, Paul Cusenza and Anne Wojcicki, who reportedly separated recently from her husband, Google co-founder Sergey Brin, the company had offered results about a customer’s risk for 254 diseases and conditions, including genes linked to diabetes, heart disease and breast cancer.

But last week, in response to the regulator’s demands, the company, based in Mountain View and backed by wealthy investors, including Google, halted television, radio and online advertising for its $99 (£60) personal genome analysis product.

The health results had marked the company out from many other direct-to-consumer genetics companies, which are largely focused on providing information about ancestry alone.

The company’s former rivals, Navigenics and deCODEme, have since disappeared from the market after being acquired by bigger companies.

But spokeswoman Catherine Afarian told US website Venturebeat: “We are not going anywhere, although we recognise that the FDA process will take time.”

And she told BBC News the company “remains committed” to consumer genetics.

Warning letter

Many of the affected customers will reportedly be able to request a full refund, although they will continue to receive raw data and ancestry information.

Ms Afarian said the company was working hard to resolve the issues with the FDA and implied it might start to reintroduce aspects of its health tests in stages.

In its warning letter, the FDA said 23andMe had not provided assurances about how well the test predicted the presence or absence of a particular genetic variant or how well that genetic variant related to the risk of a specific disease.

The FDA said it was particularly concerned about the potential health consequences of assessments for drug sensitivity and a gene called BRCA linked to breast and ovarian cancer.

“For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognise an actual risk that may exist,” the letter said.

Hank Greely, director of the Center for Law and the Biosciences at Stanford University, said the company would have to overhaul its methods for characterising genetic variants.

In a blog written at the time of the FDA order, he said: “The SNP chip method that 23andMe uses was never very good at providing useful genetic information.

“Its advantage has been its low cost. But as sequencing gets cheaper and cheaper, SNP chips have already largely become obsolete for most genetic testing.”

Anne Wojcicki has said she stands by the data, and Ms Afarian said consumers had not been harmed.

Nevertheless, the company is being sued by customers in California, who say there is “no analytical or clinical validation for the [personal genomics service] for its advertised uses”.

Invasion of the Nostril Ticks.

Tony Goldberg had been back from Uganda for only about a day when he felt a distressingly familiar itch in his nose. A veterinary epidemiologist at the University of Wisconsin, Madison, he had just spent a few weeks in Kibale National Park studying chimpanzees and how the diseases they carry might make the jump to humans. Now, he realized, he might have brought one of their parasites home with him.

There was only one way to be sure. Goldberg quickly gathered the necessary supplies—a pair of forceps, a flashlight, and a mirror—and steeled his resolve. Using the mirror to steer his hand, he poked the instrument into his irritated nostril, latched onto a suspicious lump, and quickly yanked it out, careful not to snag any nose hairs in the process. There it was: an adolescent tick. At that point, Goldberg knew, it had likely been living in his nostril for several days.

This was not Goldberg’s first nostril tick, and it’s unlikely to be his last. (On the whole, he says, the experience is “not pleasant but not as bad as you might think.”) He’s seen lots of chimpanzees with nostril ticks during his time in the field, so he’s not surprised a few of the parasites have taken advantage of his presence to burrow into the nose of a closely related primate. This particular tick, however, presented a unique opportunity. Because he found it when he was already back in his lab, Goldberg says, “I was in a position to preserve it for DNA analysis. It was just lucky that the timing was right.”

The nostril tick belonged to the genus Amblyomma, species of which are known to carry diseases that can infect mammals ranging from cows to people. But for now, that’s all Goldberg knows. “Its genetic sequence didn’t match anything in any known databases. So it could be a known species of tick that hasn’t been genetically characterized yet, or a completely new species,” he says. Goldberg reports his analysis in the latest issue of The American Journal of Tropical Medicine and Hygiene.

“It’s fun to welcome Tony to that small, elite club of publishers on ticks in the nose,” says Gary Aronsen, an anthropologist at Yale University who is one of the few other scientists to have written about a close encounter with a nostril tick. (He sneezed his out during a layover in Amsterdam and brought it home with him in a chewing gum wrapper, though he wasn’t able to sequence its DNA.) Picking up parasites like these is “part of the glory and glamour of fieldwork.”

Although researchers know very little about nostril ticks, including which other species they infest and if they carry any diseases, Goldberg speculates that his might be adapted to live in noses of chimpanzees. Chimps are fastidious groomers, so any parasite that wants to hang around for a while needs to fly under the radar. “I can’t think of a better way to do that than hide in an anatomic site that is difficult to access with the fingers,” Goldberg says. “There are several of those—some of which we won’t discuss—but the nostril certainly counts.” (In case you’re wondering, yes, chimps do pick their noses, but it doesn’t seem to dislodge the ticks.)

Because most ticks need to feed on at least three different hosts in their lifetimes, they are exceptionally good at transmitting disease. Species-jumping nostril ticks are “yet another example of how nature provides opportunities for pathogen spillover,” says tick biologist Thomas Mather of the University of Rhode Island, Kingston. Still, the thought of nostril ticks spreading throughout North America isn’t keeping him up at night. “I’m not looking at this as a likely pathway for the introduction of exotic ticks. How many ticks are going to be in a person or two’s nose?”

Nearly a year and a half after removing his own nostril tick, Goldberg hasn’t suffered any ill effects. But the parasite remains a mysterious creature, and for now, the only thing to do is wait for more specimens to turn up. He hopes his paper will raise awareness among his fellow field scientists. Soon, he suspects, “somebody somewhere will come up with another nose tick and will advance the field to the next level.”

Importance of data sharing.

Withholding information on the clinical significance of genetic variants from the scientific community impedes the progress of research and medicine.

Imagine you are a physician or researcher and seek to get more confirmation on the clinical impact of particular genetic variants. If your search of public databases comes up empty this does not necessarily mean that nothing is known about the mutations in question. Rather, the information may be locked away as a trade secret in a genetic testing company’s proprietary database.

Physicians and their patients are not able to independently verify the medical significance of a testing company’s finding, instead the results have to be taken on blind faith.  Researchers are limited in their knowledge of the vast mutational landscape in genes associated with diseases such as cancer which in turn may limit their understanding of the molecular underpinning of the disease.

Robert Nussbaum, at the University of California, San Francisco, recently pointed out that in other fields of medicine such an approach would be unthinkable. In a Technology Review he said, “Imagine if radiological images or histopathology slides of cancers were examined by a single monopoly holder without the medical community being able to assess and learn from what these images and tissue specimens teach us.” He launched  the Sharing Clinical Reports Project, an initiative to collect de-identified information on genetic testing data on the BRCA1 and 2 genes (as discussed in our August editorial).

With more genetic testing companies likely to enter the market, after the US Supreme Court invalidated some gene patents, the problems caused by proprietary data may increase. Clinicians may now have more options to obtain a genetic test, but, if they go with the less established testing company, they are then left with a suboptimal interpretation with possibly grave implications for the patient.

resolution  from the American Medical Association passed in June 2013 supports public access to genetic data. The resolution calls for companies, laboratories, researchers and providers to publicly share data on genetic variants in a manner consistent with privacy and HIPAA protections.

Whether such calls will be heeded is another question. In a New York Times OdEd piece aptly named “Our genes, their secrets” the author wonders if the recent Supreme Court decision will prompt genetic testing companies to rely more on this strategy of treating information on the clinical impact of mutations as trade secrets and thereby try to deter competition and ensure revenue.

How can this be prevented? Cook-Deegan et al.  – in a recent article in the European Journal of Human genetics – call for joint action by national health systems,  insurers, regulators, researchers, providers and patients to ensure broad access to information about the clinical significance of variants. Some of their suggestions, besides the promotion of voluntary sharing, include sharing as a condition of payment or regulatory approval of the testing laboratories.

The battle about who may offer certain genetic tests is certainly heating up. Ambry Genetics and Gene by gene, two of the companies now offering BRCA1 and 2 testing, have been sued by Myriad Genetics for patent infringement.  A few days later, on July 12, US senator Patrick Leahy, a democrat from Vermont, wrote to Francis Collins, the director of the NIH, urging him to force Myriad to license the patent on reasonable terms to other parties to ensure affordable life-saving diagnostic tests.  As the federal  agency that provided the funding for the research behind Myriad’s patent  the NIH has the authority to do so, based on a provision in the Bayh-Dole Act that enabled universities to own inventions based on federal funding. Whether it will exercise this authority is unclear. Collin’s reply is still outstanding.

Ambry Genetics disputes that it infringes any of Myriad’s patents and a company spokesperson told Nature Methods that Ambry plans to share their testing data.

If enough companies follow suit, the desirable equilibrium of compensating a company fairly for the cost of its test and at the same time letting the public benefit from the results of these tests should be within reach.



Can Doctors Predict the Future?

There are lots of myths and misconceptions surrounding personalized healthcare. Over the next few weeks, I am going to address some of these beliefs to help you better understand the truths about this exciting field.

Myth: Personalized healthcare is a “crystal ball” into my future health

Using personalized healthcare tools such as family history, doctors can predict the likelihood that you will develop a particular disease or whether a medication will be more or less effective for you. Personalized healthcare can direct your care, but it cannot predict the future with certainty.

Doctorscan look at your family health history for patterns of disease. They can use that information to assess your risk of developing diseases. If you are more likely to develop a disease, doctors can advise you about ways to slow the disease process or prevent it altogether. However, they can’t say for certain, “You will develop this disease.”

The same holds true for predicting how you will respond to medication — pharmacogenetics — although sometimes there is a more definite yes or no answer. It varies from drug to drug, and genetic testing for drugs can focus on safety, efficacy in dosing, or both.

For example, before doctors can prescribe abacavir, a drug used to treat human immunodeficiency virus (HIV) infections, patients are strongly recommended to have a specific genetic test done. This genetic test can tell if they are likely to have a hypersensitivity reaction (allergic reaction) to the drug. Because such reactions can be so severe, including death, it is important to know who can safely take abacavir.

Genetic testing for other drugs may have a different focus: efficacy. For example, clopidogrel is used to prevent blood clots in the body, and a genetic test can help determine if a patient will metabolize the drug quickly or slowly. People who metabolize the drug slowly may require a higher dose for the medication to work as intended. If these “poor metabolizers” are not identified before starting treatment with clopidogrel, they may receive too low a dose, leading to the formation of blood clots.

As you can see, personalized healthcare is not a crystal ball, but rather more like eyeglasses — it can’t predict the future, but it can help you see it more clearly!

Source: Heath Club