Proposed Guidelines on BRCA Testing Leave Many Gaps

The United States Preventive Services Task Force (USPSTF) is a government-supported independent panel of experts that reviews and develops recommendations on select preventive health services. The panel assigns letter grades to preventive services based on their opinion of strength of the research evidence. The task force just released a draft of their guidelines on genetic counseling and testing for BRCA. Despite some strengths of the updated guidelines; important gaps remain that will directly affect patient access to genetic counseling, genetic testing, and preventive services.

Significance of These Guidelines
The USPSTF published guidelines are important to consumers for two main reasons:

1. Primary care clinicians and health systems follow these guidelines. The content of the guidelines can affect what information doctors convey to patients about disease risk, screening, and prevention.
2. The panel’s guidelines must be implemented based on the Patient Protection and Affordable Care Act (PPACA), which states that health plans must provide benefits without imposing cost-sharing (i.e., without a deductible or co-pay) for services that have a rating from the task force of “A” or “B.” 

USPSTF Guidelines on BRCA Testing
In 2005, the USPSTF first issued guidelines for primary care providers on “Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility.” The task force assigned a grade “B” (recommended health care providers offer this to patients) to genetic counseling and testing for women with a family history suggestive of a possible BRCA mutation. It issued a grade “D” (recommended health care providers discourage patients from using these services) to genetic testing in women without a family history suggestive of a mutation. In 2005 this guidance was greatly needed, as many primary care providers were either unaware of BRCA testing or had received most of their information from Myriad Genetics, the laboratory that sells the test. At the time, the USPSTF did not request public or expert commentary on their guidelines.

In 2011, the USPSTF announced its plan to update these guidelines, and asked for public commentary. FORCE (and other health care experts) submitted written recommendations to the USPSTF on its plan to review the research on BRCA genetic counseling and testing and update the guidelines. Despite receiving extensive suggestions for strengthening and improving the guidelines, last month the USPSTF released new draft guidelines that essentially restate the 2005 guidelines and grades with few changes. In general, I agree with the letter grades that were assigned, but I’m disappointed that this opportunity for guideline revision was not used to address critical gaps. With the recent passage of the PPACA—which references USPSTF guidelines to determine insurance coverage of some preventive services—it is more important than ever that the USPSTF guidelines on genetic counseling and testing are practical, comprehensive and evidence-based. Gaps in the guidelines will now directly affect patient access to genetic counseling, testing, and preventive services as outlined by this new legislation.

An overview of our comments is available on our advocacy page, and our full written comments as submitted to the USPSTF can be viewed here.

FORCE Concerns with the Draft Guidelines

• The patient population covered by the guidelines is too narrow. Important groups are not specifically included in the USPSTF guideline “B” letter grade:
  • Women who have been diagnosed with cancer
  • Women with a known BRCA mutation in the family
  • Women with a family history of cancers other than breast or ovarian cancer that puts them at high risk for inherited cancer
  • Men

• No letter grade is assigned to any risk-management options.
  The task force mentions risk-management interventions but does not assign letter grades to specific prevention and screening options. With no letter grade assigned, these preventive services are not guaranteed coverage under the PPACA, nor will health plans be directed to provide the services without out-of-pocket costs to patients.

• The current guidelines take a single-syndrome approach to family history and genetics. The task force states: “…primary care providers should ask about specific types of cancer, which family members were affected, and the age and sex of affected family members…For women who have positive family histories of breast or ovarian cancer, primary care providers may use one of several brief familial risk stratification tools to determine the need for in-depth genetic counseling.”

Encouraging doctors to take a patient’s family history of breast and ovarian cancer is a positive step. However, the guidelines only provide instructions for referring women with a positive family history of these two cancers. Other cancers (such as pancreatic cancer) can be associated with a BRCA mutation in a family. Further, a family history of different cancers may indicate other hereditary syndromes associated with different mutations than BRCA. Lynch Syndrome, for example, is associated with a family history of ovarian, colon, and/or endometrial cancers and Cowden Syndrome is associated with breast, thyroid, and uterine cancers.

FORCE Recommendations to the USPSTF
FORCE’s submitted recommendations for addressing these gaps, focusing on issues that we felt had the most supportive research evidence:

• Extend the evaluation and letter grade to women with a known mutation in the family
• Extend the evaluation and letter grade to women who have been diagnosed with breast cancer and who meet criteria based on personal and family history of cancer 
• Assign a letter grade to the following risk-management options
  • Breast MRI 
  • Risk-reducing  bilateral mastectomy
  • Risk-reducing bilateral salpingo-oophorectomy
  • Oral contraceptives
• Review the evidence and develop one set of integrated practice guidelines for collecting family history and referral of appropriate individuals for genetic counseling, testing, and related preventive services. These guidelines should include Lynch Syndrome and other relevant hereditary cancer syndromes.

Guidelines Are Important, But A New Approach Is Needed
Focusing public health efforts on disease preventive is lifesaving. Applying risk assessment allows us to better tailor prevention and screening for those in the highest risk categories; this approach is both lifesaving and cost saving. Developing expert guidelines based on  the strength of research on preventive care is worthwhile. But we must do a better job in guiding primary care doctors specifically on topics of genetics, risk assessment, screening, and prevention of hereditary disease in order to save more lives.

The USPSTF consists primarily of public health experts rather than clinical experts in disease and genetics. This may not be the best approach for reviewing topics in the realm of personalized medicine and genetics. The Centers for Disease Control (CDC) Office of Public Health Genomics organizes a panel – the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group – which includes both public health experts and clinicians. EGAPP provides an example of a more inclusive panel for reviewing the application of genetics to public health.

The narrow approach of reviewing research for only one hereditary cancer syndrome and only specific portions of the community while ignoring other hereditary syndromes and populations at risk does not serve the public well. Using this approach, the USPSTF is missing the opportunity to help practitioners identify people at very high risk for many preventable diseases with a goal of saving lives. Health care professionals and the public would be better served by having a single set of evidence-based guidelines that address the collection and evaluation of personal and family medical history to identify people who would benefit from genetic counseling and testing for many hereditary diseases. These guidelines should include all hereditary disease syndromes and conditions that have associated genetics tests with clinical utility.

FORCE plans to work with policy-makers and other advocacy groups to outline and propose a new approach to systematic review of preventive services such as collection of family history, genetic counseling, genetic testing, and screening and prevention options. Our goal will be to address important issues including:

• Determining which experts should be included on preventive services task force panels
• Prioritizing the diseases and preventive services to be evaluated
• Integrating the guidelines for different diseases and services into a single set of easy-to-follow recommendations on risk-assessment, screening, and prevention
• Expanding coverage under the PPACA, Medicare, and Medicaid for preventive services for more diseases, populations, and medical interventions

The new USPSTF draft guidelines highlight gaps in education resources, research and access to care. There is a continued need for FORCE to take action and unite our community to advocate for more HBOC-specific research and more access to credible information, genetic counseling and testing, and risk-management options. At the same time, FORCE will be working with groups representing other hereditary diseases to address the global issue of how to better incorporate personalized medicine and genomics into public health. Stay tuned for updates.

Gene Discovery, Patents, and the Community

Recently a dear friend sent me a link to an article in the February 1996 issue of Nature Medicine. The article by journalist Adam Marcus covered a media event and panel of women’s rights advocates expressing concern about Myriad’s impending patenting of the BRCA1 gene. Panelists declared unregulated genetic testing to be the coming century’s foremost threat to individual liberty. Incredibly, 17 years after the publication of Adam Marcus’ article, the debate is still ongoing—the issue of gene patenting and the consequences of lacking regulation regarding gene patents are still present and as relevant as they were then.

Admittedly, I missed this article the first time around. In 1996, I was more likely to be reading the Journal of the American Veterinary Medical Association than a human medical journal. With a toddler, a budding veterinary career, and no significant family history of breast cancer, my focus was not on hereditary cancer. In fact, genetic testing and gene patents were furthest from my mind. But my diagnosis with breast cancer eight months later and subsequent revelation that I have a BRCA2 mutation changed that.

When I was first tested for a BRCA mutation in 1998, I was fortunate; my testing costs were covered by my health insurance. I was very grateful to have access to the test; my gratitude extended to the laboratory that made the test available to me. Although I was initially tested without genetic counseling, I went to MD Anderson Cancer Center for a second opinion and eventually found my way to a genetics expert and had access to up-to-date and credible information from experts. It wasn’t until I became immersed in my work with FORCE that I became aware of deeper issues that were the consequence of Myriad holding patents on the BRCA genes.

In 2009, Joanna Rudnick released her documentary In the Family, which shined a spotlight on Myriad’s gene patents and some of these consequences. The documentary included an eye-opening interview with Dr. Mark Skolnick, founder of Myriad Genetics. Joanna questions how a gene—a product of nature—can be patented, saying “It’s like patenting your thumb.” Skolnick compares Myriad’s patents on the BRCA genes to patents for ipods, telephones, and computers, and cavalierly asserts “there’s no controversial patent. It’s all very easy to understand if you take the time.”

In the film, Joanna brilliantly follows the Myriad interview with an interview of Dr. Mary-Claire King, who was credited with identifying the location of the BRCA gene when she was a researcher at University of California at Berkeley. Dr. King has dedicated herself to the research that proved the existence of hereditary breast cancer gene mutations. Her research laid groundwork that sent many laboratories racing to be the first to isolate and clone the gene for genetic testing.

In Rudnick’s film, Dr. Skolnick says, “I think the single greatest inventive thing I did was to create Myriad. We did it to win the race…and we won.” Asked point-blank why the cost of the test is increasing, Dr. Skolnick replies, “that’s a good question, and I think there’s a point at which we have to start looking at decreasing the cost of the test.” Yet, four years after the documentary was released, the cost of testing has gone up—BRCA testing is more expensive, even though the technology for sequencing DNA has become less expensive.

The gist of Dr. King’s interview starkly contrasts with Dr. Skolnick’s statements. Dr. King speaks about genes for which she holds patents, saying, “The critical thing about the patents we hold is that none of them are exclusively licensed. So they are completely open for anyone to use for research purposes and any company that wishes to license them can license them for a trivial amount of money.” King mentions that her last royalty check amounted to $2.73. In contrast, the February 6 edition of the Salt Lake Tribune reports Myriad’s earnings: ”Myriad projects full-year 2013 revenue will fall between $575 million and $585 million. That would be a 16 percent to 18 percent increase over fiscal 2012.” The contrast is apparent and appalling.

Over the years, FORCE has appealed to government agencies and spoken to the health care community and the public regarding Myriad’s exclusive patent, and explained how the corporation’s marketing strategies and policies have increased the burden on the hereditary cancer community that we serve. In 2008 and again in 2009 we testified to the Secretary’s Advisory Committee on Genetics Health and Society, expressing our concerns with direct-to-consumer marketing of genetic tests, and specifically Myriad’s marketing practices, which we feel encourages BRCA testing without first receiving genetic counseling from qualified experts trained in cancer genetics. In our opinion, their aggressive marketing strategies have been harmful to members of our community.

In 2009, the American Civil Liberties Union filed a lawsuit challenging Myriad’s patents on the BRCA genes. On April 15, 2013 the U.S. Supreme Court will hear oral arguments on gene patenting. This hearing will represent the culmination of four years of the legal tug-of-war between Myriad Genetics and the plaintiffs, which included the ACLU and a long list of individual, advocacy, and health care professional groups. FORCE agrees with the ACLU that exclusive gene patents negatively affect access to care and research and we have filed an Amicus (Friend of the Court) brief on behalf of plaintiffs. You can read our testimony to the United States Patent and Trademark Office on the topic of how exclusive gene patenting impacts research and access to care. The Supreme Court oral arguments will be open to public participation.

For those who wish to learn more about Dr. King’s work, Decoding Annie Parker is a new  movie that follows the parallel lives of Dr. King and Annie Parker, a Canadian woman whose family was impacted by hereditary cancer. Based on a true story, the film raises the profile of Dr. King’s contribution to the discovery of hereditary breast and ovarian cancer syndrome and the BRCA1 gene mutation. It is sure to resonate with many in our community. FORCE is a proud charity partner of the movie, which stars Helen Hunt as Dr. King. A special screening will be held April 2 in New York City. FORCE will hold  screenings of the film in other cities. Stay tuned for updates.

Applying Personalized Medicine to Disease Screening and Prevention

Personalized medicine uses information about an individual’s genetic make-up to deliver the right screening, prevention, or treatment options at the right time to achieve the best medical outcome. Genetic counseling, risk assessment, and genetic testing to determine inherited predisposition for diseases are important and growing areas of personalized medicine that further this goal.

Critics have raised concerns that identifying and treating people who are at risk for disease necessarily leads to “over-medicalization” of health care and increases cost and the possibility of causing harm. Evaluating the risks and costs versus benefits of disease prevention and control, however, is complex and depends on the disease in question, available screening and risk-management options, individuals or populations who are most at risk, and their level of risk for the disease. Given our limited resources and focus on containing health care costs, we will move beyond a one-size-fits-all approach to health only when we are willing to carefully consider each of these variables, rather than discounting all risk assessment, screening and prevention as over-treatment.

Not all risk is the same
Risk changes over the course of a lifetime, depending on genetics, lifestyle and other factors. Preventive care and screening recommendations for people of average risk are based on studies of thousands of people in the general population—sometimes they are not adequate for people who have a higher risk for a particular disease. Personalized medicine allows us to identify people with higher-than-average risk and provide interventions that can improve their health outcomes. For example, the American Cancer Society recommends annual mammograms beginning at age 40 for women with an average risk for breast cancer. But women with BRCA mutations, who face a higher lifetime risk for breast cancer at a younger age, and tumors that may develop faster and more aggressively, need more frequent and rigorous screening that begins at an earlier age and involves annual MRI surveillance.

Not all diseases are the same
Diseases develop and behave differently and have different impact, morbidity, and mortality, which must be considered when weighing the cost and risks compared to the value of screening and prevention. Impact of a disease includes the number of people affected and the consequences of diagnosis and treatment on survival and quality of life. Basal cell skin cancer and ovarian cancer illustrate these differences.

Roughly 2.8 million people in the United States are diagnosed with basal cell skin cancer yearly, compared to about 22,000 ovarian cancer diagnoses. Basal cell cancers can be detected through skin exams, and almost all cases are cured. With no reliable detection or screening, ovarian cancer is most often found late, when the five-year cure rate is less than 50%. Ovarian cancer patients require extensive surgery, chemotherapy, and sometimes radiation, often with profound negative effects on quality-of-life. Although more people are affected by basal cell cancer, more people die of ovarian cancer. Screening and prevention recommendations for a common, detectable, and treatable disease like basal cell cancer require different considerations than those for a less common cancer (like ovarian cancer) that cannot be detected early, carries a poor prognosis, and is accompanied by aggressive treatment. It makes sense to focus efforts and apply technology to identify those in the highest risk category for deadly diseases such as ovarian cancer and prevent them whenever possible.

Not all interventions have the same risks or benefits for everyone
We can predict risk for some diseases like Huntington’s, for which we have no effective or proven intervention. However, many diseases, such as breast cancer, have interventions that lower the risk for or improve the odds of detecting the disease at it’s earliest and most treatable stage. Each disease intervention option has unique risks, costs, and benefits that should be considered individually.

MRI is a sensitive tool that can detect breast cancers that are too small for a mammogram to find. But MRI screenings are expensive, and they often find suspicious but harmless breast changes, requiring a biopsy to assure that they are benign. For these reasons, experts don’t recommend screening breast MRI for women of average risk for breast cancer. Women at high risk have a greater likelihood of an abnormality being actual cancer, and that often tips the scales in favor of increased surveillance, even if that means a greater chance of needing a biopsy. Long-term research on high-risk women shows that MRI detects breast cancers at an earlier stage resulting in less extensive treatment.

Having a BRCA mutation raises the lifetime risk for ovarian cancer up to 50%, compared to 1.5% for women with average risk. Prophylactic bilateral salpingo-oophorectomy (removal of the ovaries and tubes) is the most effective way to reduce ovarian cancer risk, but like all surgery, the procedure has its own potential for risk and harms: complications from anesthesia, infection, and early menopause, which can be associated with long-term health and quality-of-life consequences. Surgery is also costly. On the other hand, research has shown that BSO improves survival in high-risk women. Given the costs, risks, and benefits of prophylactic surgery versus the consequences of an ovarian cancer diagnosis, this intervention offers more value to women at very high risk and less value to average risk women.

Research shows that prostate cancer screening using PSA increases detection of this cancer but may not improve survival for many men. PSA screening has risks and limitations including: many of the cancers found are not symptomatic and will not affect life-span or quality-of-life; PSA tests can yield many false-positive results leading to unnecessary biopsies; treatment of prostate cancer can lead to side effects in many patients. Given this, the United States Preventive Services Task Force (USPSTF) issued guidelines that recommended against PSA screening for men of average risk. However, recent research suggests that men with BRCA 2 mutations face a higher lifetime risk for more aggressive, younger-onset, prostate cancer than men in the general population. Applying personalized medicine to their guidelines, the USPSTF qualified that “This recommendation…does not consider PSA-based testing in men with known BRCA gene mutations who may be at increased risk for prostate cancer.” 

Not all information is clinically useful
Before BRCA mutations were identified, individuals with a strong family history of cancer had no way to know whether they had inherited a very high risk for cancer. Basing their risk on family history alone, these women sometimes pursued prophylactic surgery, even though their lifetime risk was no higher than the average woman’s. The availability of BRCA testing improves decision-making for high-risk women, giving them the opportunity to learn more about their personal risk and make evidence-based health care decisions.

The same advances that make BRCA genetic testing possible have also led to the development of other tests that may not be as useful. Genetic testing allows researchers to understand how diseases develop and design better options for screening, prevention and treatment. But not all genetic tests should be offered to the general public for decision-making purposes; particularly those that do not provide “actionable” information that people can use to improve their health or quality of life.

Informed decision-making
Given credible information, people are capable of weighing the costs, harms, and benefits of different medical interventions. Genetics experts can help to guide people through the maze of factors described in this blog to make personal informed decisions about their care.

BRCA is just the tip-of-the-personalized medicine iceberg. Genetic tests have been developed that can look at tumor cells to determine the best treatment or predict the likelihood of people having side-effects from a particular therapy.  Granted, personalized medicine is not an exact science, and we are not yet able to apply it to all people and all diseases. But it makes sense to use evidence-based interventions to save and improve the quality of as many lives as we can. As a society, we need to continue to invest in the research, translation, and application of personalized medicine, risk assessment, and genetic testing to determine the best candidates for the best interventions at the best time.

13 Facts that Men with Hereditary Cancer Risk Should Know

As we approach Father’s Day we would like to call attention to an often forgotten group: men who have a BRCA mutation or a family history of hereditary cancer. Although men don’t get ovarian cancer and their risk for breast cancer is very low, we are learning more and more about how hereditary cancer risk affects them.

FORCE responded to the United States Preventive Services Task Force’s (USPSTF) preliminary guidelines that recommended against prostate cancer screening for all men. Based on emerging research, we encouraged the panel to revise the text to state that the guidelines did not apply to men with BRCA mutations. The USPSTF incorporated our suggestion into its final guidelines. Accomplishments like these remind us how important FORCE’s advocacy work is. Men with BRCA mutations are important cancer stakeholders. Our goal is to assure that they have a voice advocating for their concerns when government cancer policies are developed.

In keeping with our 13 Things theme and in honor of high-risk men, here are 13 facts men need to know about hereditary breast and ovarian cancer.

1. Men with BRCA mutations have increased risk for breast and prostate cancer, and like women with mutations, their risk for pancreatic cancer and melanoma is also elevated. Men with BRCA2 mutations have greater risk than men with BRCA1 mutations.
2. Although men with BRCA mutations have a greater cancer risk than men in the general population, their risk for cancer is lower than most women with a mutation.
3. Because preliminary research suggests that hereditary prostate cancer tends to be a more aggressive form of the disease, the USPSTF advises that screening guidelines developed for men in the general population should not be applied to men with mutations.
4. BRCA mutations have been found in people of every ethnicity, but not with the same frequency. About 1 in every 300 to 500 people carry a BRCA mutation. About 1 in 40 people of Ashkenazi Jewish descent have a mutation.
5. Breast screening recommendations for men with a mutation include regular breast self exams and twice yearly clinical exams by a medical professional beginning at age 35. A baseline mammogram is recommended at age 40 and annual mammograms thereafter are advised, depending on the baseline results.
6. Men with mutations or hereditary cancer in the family should discuss with their doctor the benefits, limitations, and risks of prostate screening using PSA and digital-rectal exam beginning at age 40.
7. The international IMPACT study is looking at the benefit of PSA screening in men with and without BRCA mutations. Full results from this research will be available in 2020.
8. BRCA mutations can be passed down equally from either parent to sons or daughters.
9. When both parents have a BRCA2 mutation, their children may inherit a rare and deadly disease known as Fanconi Anemia. This is more common in people of Jewish descent. Couples concerned about this possibility should consult with a genetics expert.
10. Couples who are concerned about passing a mutation to their children may want to speak with a fertility expert about in vitro fertilization and preimplantation genetic diagnosis that screens embryos for BRCA mutations.
11. Early research on PARP inhibitors for treatment of prostate cancer has been promising. Currently, some open PARP inhibitor studies are enrolling men with advanced prostate cancer.
12. Coverage for BRCA testing in men can vary depending on their insurance plan. A genetic counselor can help men determine if their insurance will cover testing.
13. Men who are concerned that the cancer in their family may be hereditary should consult with a genetics expert before pursuing genetic testing. FORCE can provide information on locating genetics specialists. Genetics consultations are typically covered by insurance.

If you are a man with a BRCA mutation or hereditary cancer in your family, please complete our survey for high-risk men, read about our advocacy efforts on behalf of the men in our community, visit our expert-reviewed information section for men, and join our mailing list to stay updated on new information, research, and programs specific to men with BRCA mutations. Please consider participating in this telephone focus group research study for high risk men.

FORCE helped unite and organize the female hereditary cancer previvor and survivor populations to advocate for more resources; we need to do the same for the men in our community. If you have high-risk men in your life, please let them know about these resources. Please help us raise awareness, spread the word, and save lives by sharing this blog, and printing and sharing our “13 Things Men Need to Know” flier.

Exclusive gene patent on BRCA: Adding burden to an already overburdened community

The United States Patent and Trademark Office (USPTO) is gathering information on the impact of gene patenting on genetic diagnostic in order to prepare a report to Congress under the America Invents Act. The USPTO is soliciting public commentary on this important issue by organizing public hearings. This past Thursday, Lisa Schlager, Vice President of Community Affairs and Public Policy testified on our behalf. It is our position that the awarding of an exclusive patent for the BRCA 1 and BRCA 2 gene to Myriad Genetics has adversely affected access to care and research specific to hereditary breast and ovarian cancer adding additional burden to our already overburdened hereditary cancer community. You can read our more on our testimony here and our summary on the issue on our USPTO advocacy page.

In our thirteen years of advocating for and serving the hereditary cancer community, we have seen firsthand the adverse affects from exclusive gene patenting. We testified that:

• Exclusive licensing of BRCA testing stifles research, including:
  • Research on PARP inhibitors, targeted therapy for BRCA-associated cancer: 
    Although PARP inhibitor research has been promising, seven years later the drugs have yet to gain FDA approval.  In a meeting with the FDA, FORCE was told that for targeted therapies that benefit a distinct population, (such as people with a BRCA mutation) to gain FDA approval, any companion laboratory test identifying the target population must be FDA approved as well. BRACAnalysis—Myriad’s test for BRCA mutations is NOT FDA approved. Myriad is a CLIA‐approved laboratory; they were never required to receive FDA approval in order to market their test, and it doesn’t appear that they currently have plans to seek FDA approval. Because Myriad holds the patent on the gene, no other lab can develop an FDA‐approved test to identify BRCA mutation carriers.  As a result, drug companies have opened up registration studies for the wider breast and ovarian cancer populations—comprised mostly of people who do not carry BRCA mutations. The two largest registration trials didn’t meet primary end‐points, likely due to the broader study population chosen. This has delayed development and approval of these agents.
  • Research that helps determine which BRCA genetic changes are deleterious and which are not
    BIC (Breast Information Core) is a large international consortium organized by the National Human Genome Research Institute (NHGRI), which is part of the National Institutes of Health.  BIC’s goal is to provide critical research to determine gene changes that may be cancer‐causing vs. those which aren’t. Around 2004, Myriad stopped contributing data to the BIC database.  About 7% of BRCA tests return with an inconclusive result and data from BIC is used to help better classify these variants to determine if they are cancer‐causing. According to a 2010 article in the Genomics Law Report, the company [Myriad] quietly stopped contributing data [to BIC] in favor of building its own database to retain a competitive advantage over other gene testing companies once their patent runs out.
• Exclusive licensing negatively impacts BRCA test interpretation
  Myriad no longer contributing to the BIC database has impeded the interpretation of a type of test known as a Variant of Uncertain Significance (VUS). Once the patent does expire, the fact that Myriad no longer contributes mutation information to the BIC consortium will limit other laboratories’ ability to interpret certain test results. According to a 2011 article from the New York Times, withholding this data may provide a competitive benefit to Myriad over other laboratories after their patent expires. But it comes at the cost of critical information that could help provide information to families that have inconclusive genetic test results right now.
  
• The excessive cost of testing limits access and negatively affects clinical care
  There is now evidence-based information demonstrating that identifying those who have the highest risk for breast and ovarian cancer can lower breast, ovarian, and all-cause mortality through genetic testing and surgical prevention. The cost of prevention, both in dollars and human lives, is less than the cost of treating cancer once it is diagnosed. Yet, people are being denied access to critical health information due to the excessive cost of BRCA testing. Financial assistance for BRCA testing is limited, especially for people who have any type of health insurance.With patent exclusivity and a monopoly on the test, Myriad has increased the cost of their test even as the cost of genetic technology and gene sequencing has gone down. Due to the exorbitant price, some insurers are no longer covering the cost of BRCA testing.

FORCE asked the USPTO to place a moratorium on issuing further gene patents until the impact on access to care and research had been better studied. Additionally, in 2010, the Secretary’s Advisory Committee on Genetics Health and Society (a panel of experts convened through NIH to report to the Secretary of Health on issues related to genetics and health care) submitted a report to Secretary of Health Sebelius on the topic of gene patenting. We encouraged the USPTO to adopt, or at the very least, to cite the SACGHS recommendations when reporting to Congress on the results of their hearings.

The USPTO will be convening a second public hearing on Friday, March 9, 2012, beginning at 9 a.m., Pacific Standard Time (PST), and ending at 4 p.m. in San Diego, California. Testimony from both hearings will be available via webcast on the USPTO website. They are also accepting written public commentary sent by email to genetest@uspto.gov.

We would like to hear what you think about this issue. Please fill out our short survey and share your opinions on the impact of exclusive patents on BRCA or other genes.

Advocating for Men: Responding to the USPSTF Recommendations against PSA

I am concerned both on a professional and personal level about the United States Preventive Services Task Force (USPSTF) recent draft guidelines that recommend against PSA screening for men of average risk or who are high risk by virtue of a family history of cancer. FORCE has prepared a position statement in response to this draft and we are encouraging our members to read our statement and submit commentary to the USPSTF.

My father died of prostate cancer. No matter how much I told him about BRCA, the hereditary cancer link, and his own risk for cancer, he ignored his health and refused to get checked. When he developed a severe case of pneumonia that put him in the hospital, he had his first physical exam and blood work in 35 years. His PSA was elevated. Only after he had serious symptoms did he finally agree to a biopsy; by then the prostate cancer was advanced. It took his life the following year. I have two brothers and worry about them. Like most parents with a BRCA mutation, I also worry about whether or not I passed my mutation on to my son.

Although it is true that men with mutations do not have the same extraordinary high risk as women with mutations, men do have a very elevated lifetime risk, as high as 33%. Like other cancers in mutation carriers, BRCA-associated prostate cancers are different than sporadic prostate cancers. In men without mutations, prostate cancers are often slow in onset, asymptomatic, and may never progress or affect quality-of-life or lifespan. Recent research, however, shows that men with BRCA2 mutations who develop prostate cancer are more likely to develop cancer at a younger age, have an aggressive form, and die of the disease compared to those in the general population. So guidelines for prostate cancer screening for the general population may not apply to those with mutations. The ongoing IMPACT study, an international collaboration, is looking at whether PSA can improve detection of prostate cancer and survival in mutation carriers.

In drafting their latest recommendations, the United States Preventive Services Task Force (USPSTF) did not take into account any of the published studies that relate specifically to men with mutations. FORCE plans to submit our position statement to the USPSTF, strongly urging that the guidelines be revised to clarify that they are not meant for men who have a BRCA mutation or a high likelihood of carrying a mutation. Please read our full position statement on the guidelines. The USPSTF  is accepting public comments on the proposed guidelines until November 10. We have a chance to influence the final recommendation so that it takes into account high-risk men with mutations. Let’s advocate for the men in our community and help save lives!

If you are a man with a BRCA mutation and you are interested in participating, visit the IMPACT study website.

The community speaks out! Your thoughts on the USPSTF breast screening guideline changes.

Newly-recommended changes for breast cancer screening by the United States Preventive Services Task Force (USPSTF) are getting a lot of attention and proving to be controversial. The task force:

• Recommended against screening mammography for women ages 40–49.
• Recommended screening mammography in women older than 50 be performed  biennially rather than annually.
• Recommended against teaching or performing Breast Self Exam (BSE) at any age.

FORCE disagrees with these screening guideline changes and believes they will cost lives, lead to confusion, worsen already existing health care disparities, make it more difficult for women to weigh the benefits and risks of screening for themselves, and make it more difficult to get insurance reimbursement for screening.  We strongly encourage the government and health care community to ensure that all women have access to risk assessment expertise and tools that allow them to understand their personal risks make informed decisions about their care.

The USPSTF recommendations specifically apply to women of average risk, but these changes will also detrimentally affect members of the high-risk community we serve.

FORCE has published a statement on these guidelines which we are asking our community to read. If you agree with our statement you can also sign our petition and provide us with feedback on your personal experience and let your voice be heard.

Because of underutilization of genetics experts and risk-assessment tools, many people learn about their high-risk status only AFTER THEY ARE DIAGNOSED with breast cancer, detected either by mammogram or breast self-exam.  For this segment of our community, access to surveillance is critically important; these guideline changes will needlessly cost lives.

The following personal experiences from members of our community  reinforce our position. Many individuals indicated that their high-risk status was not identified until after a diagnosis.  Without access to breast screening their cancer would have likely been discovered at a more advanced stage and they may not have survived.

 “My breast cancer was found on a mammogram at age 33.  I only began having mammograms after finding a lump on breast self exam. There was no family history of breast cancer or anything to indicate that I was high risk until after my diagnosis.  Subsequently I learned that I had a BRCA2 mutation.”

“When I was in my 20s I was not considered high risk and was told to watch and wait to see what happened with a lump I was concerned with.  Thankfully it was nothing.  However, today I am considered high risk due to a [mutation in] BRCA1 and I am eligible for screening. I am the same person with the same genetic background but the recommended course of action varied with the label.  How many women in their 40s are there like me?”

 “I found my own lump at the age of 33 via breast self exam.  This quite literally saved my life.  I subsequently learned that I am BRCA1–but had no known family history of breast or ovarian cancer beyond a paternal grandmother who died before I was born.  Without having done this routine self exam, I would not have found the lump when I did.” 

“My 47-year-old sister was diagnosed by mammogram with breast cance;, tumors appearing in both breasts.  We have NO family history, therefore she was being screened based on recommendations that women in their 40s start mammograms.  We have since found out our family carries the BRCA2 mutation.”

“With no close family history of breast cancer, I was 41 and going through fertility treatment.  I had no idea that I might have a genetic mutation that would cause me to have breast cancer.  I decided to get a mammogram before being implanted with embryos.  It was that mammogram that found a 2.5cm tumor in my right breast.  Even the surgeon said that she wouldn’t have found it if it hadn’t been for the mammogram.  If I’d been forced to wait until I was 50 for this test, I would be dead now.”

“My aunt was diagnosed with breast cancer at age 42. Her sister was diagnosed in her 50′s. We now know we carry the BRCA 2 gene mutation, but we didn’t know when my aunts were diagnosed. How many high risk people, who don’t know they are high risk, will get cancer at a young age and have it go undetected because they didn’t have routine screenings if policies change?”

One task force concern was that women ages 40-49 who are routinely screened are more likely to undergo multiple biopsies which are usually negative. Yet many women, particularly those in the FORCE community, feel that the risk of missing a single breast cancer far outweighs the risk of potential additional biopsies. Here are some additional comments from our members:

“I am appalled at the suggestion that it is too stressful for women to deal with false-positives—I had a false positive and the “stress” was (1) better than finding out that it was not a false-positive and (2) worth the life of that one woman in 1900. We do not have to be protected from too much “stress” by this panel or anyone. What we need is to continue lowering the breast cancer death rate.”

“As high-risk women we know anxiety well and find a way to deal with it. Let US decide what anxiety we want to deal with. I’d rather have anxiety and be screened than live in ignorant (but possibly deadly) bliss.”

“Ever not been anxious over a mammo or a biopsy? But, I would rather be anxious about results than to trust that I won’t be one of the 1 out of 1900 women whose BC is missed by having no mammo[gram]. How many people here have died from anxiety? And how many have died from undetected breast cancer?”

“Years before I was diagnosed with breast cancer, I had a biopsy that was negative. The stress of the biopsy was nothing compared to the anxiety I felt after my diagnosis of breast cancer. For me, I would trade the stress of biopsies to assure that any cancer was caught early.  I am glad that I was able to make that decision for myself.”    

Your stories reinforce what we already know: mammography in young women does save lives. We must apply all the means we have to save as many lives as we can. Even the task force agrees that the research shows that mammograms save lives.  However, their conclusion is that the cost/benefit ratio doesn’t justify continued screenings for women ages 40-49 orannual screenings for women after age 50. Your stories tell the personal stories of women diagnosed young, and women diagnosed with aggressive cancers that would have progressed had these new guidelines been in practice. 

“My stage 2A breast cancer was caught on a routine SCREENING mammogram when I was 44.  I had no lump that I could feel, yet the tumor was 3.2 cm.  My OB/GYN did not feel the lump during a clinical breast exam 4 months prior to the mammogram. I do not have a BRCA gene mutation, and the genetic counselor said my risk of getting breast cancer was no higher than that of the general population.”

“I was diagnosed with high-grade DCIS by routine mammogram.  I am 47 years old and would fall out of the guidelines. I cannot imagine what would happen in those 3 years.  A mammogram is such a noninvasive relatively inexpensive test that can be a lifesaver.”

 “I was diagnosed with breast cancer found in my baseline mammogram.  I did not know that I carried the BRCA2 mutation that predisposes me to cancer.  Had these guidelines been the standard at that time, I doubt I would be a 10-year breast cancer survivor.  Scientific findings are one thing, but I am the 1 in 1900 who did have breast cancer found on a mammogram before the age of 50.  I shudder to think what might have happened to me if insurance plans were following guidelines such as the ones presented by the USPSTF.”

 “My breast cancer was caught by a mammogram at age 47; my sisters at age 40.  Because of mammography, our cancers were caught early.”

“My premenopausal breast cancer was caught early on a mammogram.  And although it was mostly DCIS, there was an invasive component to it and it was in my lymph nodes. Had my diagnosis been delayed even a year, it likely would have spread beyond lymph nodes.”

The task force concluded that the harms of breast self exam outweigh the benefits in women of any age.  Once again we disagree with their conclusion. Your stories have validated our concern with these guideline changes. We believe that breast self exam can help identify breast cancer and likely saves lives.

“My breast cancer was stage 1 because I caught it via BSE at age 36. My gynecologist had performed a clinical breast exam just 6 weeks prior to my finding the lump, and found nothing. I am absolutely sure that BSE saved my life.”

 “I had a breast exam by a doctor in my annual exam, a few months before I found a 2.5 cm lump myself, undetected by the doctor. My self exam saved my life, I had a very aggressive and fast-growing cancer. Had I waited until my next annual exam for a doctor to check for lumps, I’m sure my cancer would have spread.”

“I was 52 when I discovered a lump doing a breast self exam.  I had a mammogram just 3 months before.  I know many women in their 40s who have been diagnosed with early -stage breast cancer. If not for self exams and mammograms, they might not be here today.”

“Self exam discovered aggressive BC between mammos at age 40.  Because I had been getting mammograms, I was aware and doing self exams.  Mammos and self exam saved my life.”

“I found my own lump at the age of 33 via breast self exam.  This quite literally saved my life.  I subsequently learned that I am BRCA1–but have no known family history of breast or ovarian cancer beyond a paternal grandmother who died before I was born.  Without having done this routine self exam, I would not have found the lump when I did.  Mammography subsequently showed the presence of an additional, deeper tumor in the same breast.  I am LUCKY to be alive today –and if I had not found the lump through self exam, I would not be here.”

“I was 24 when I did a self exam and found a 3cm tumor of aggressive breast cancer. Breast self exams are EXTREMLY important for women of all ages.

The task force review of risk/cost/benefit for breast cancer screening highlights the need for better, more effective breast cancer screening, the importance of better utilization of risk-assessment tools currently available, and the need for more research on risk factors, screening, and outcomes. Considering current concerns about  health care costs, guideline reviews and changes like these mandate that we do a better job in assessing women’s risk for breast cancer to more effectively allocate resources. In an age where more personalized medicine is within our grasp, we should strive to replace sweeping one-size-fits-all recommendations with better risk assessment and appropriate screening recommendations based on risk.  For those found to be in average or lower-risk categories—until risk assessment is an exact science—each individual should have access to credible and balanced information and be allowed to weigh the benefits and risks and decide what makes sense for them.

Direct-to-consumer genetic testing: the latest FORCE testimony to SACGHS and FDA feedback

Recently FORCE submitted testimony to the Secretary’s Advisory Committee on Genetics Health and Society (SACGHS) about our continuing concerns about the need for government oversight of the marketing of genetic tests to consumers and health care providers.  Below is an excerpt from our testimony.

Dear Distinguished members of the committee, I represent the lay advocacy group, Facing Our Risk of Cancer Empowered (FORCE), a national 501(c)3 nonprofit organization whose mission is to improve the lives of individuals and families affected by hereditary breast and ovarian cancer. I am here to follow up on the testimony presented last year to this committee by Dr. Sue Friedman, our Executive Director and present our mounting concerns about the unrestricted marketing that is being used by genetics laboratories and specifically Myriad Genetics. I would like to share with you how these actions are impacting members of the community that we serve. As Sue Friedman testified at the last meeting, based on what we have witnessed it is our opinion and belief that Myriad’s sales representatives discourage doctors and other health care providers from referring patients to genetics experts.

In the past, Myriad has denied use of such a strategy, and when presented with our concerns their Vice President of Marketing dismissed them as the work of a few “rogue” sales agents. However, in a recent publication, Myriad CEO Peter Meldrum was quoted as saying that Myriad’s sales force “provides doctors [with] the tools to do counseling” in-house, and as a result, physicians can bill insurers directly for the service.”

The same report stated that:

“Helping doctors to set up genetic counseling services in their own practices is a priority for the Myriad sales team, which is currently 300 reps strong, ahead of a direct-to-consumer effort in a particular geographic region. The company has carried out DTC ads in the Northeast and the Midwest, and is continuing marketing efforts in the South. According to Meldrum, sales representatives educate doctors and nurses about who should be tested on BRACAnalysis and how to handle patients’ questions about genetic risk. Also, the company’s sales reps attempt to reach doctors and show them DTC ads for BRACAnalysis ahead of its television airing in a particular locale, so they can be more prepared when patients come into their offices asking about the test.”

Having reviewed Myriad’s education materials for health care professionals, we are concerned that they focus only on the hereditary syndromes for which the lab markets a test. Unfortunately, we believe these materials are misleading and in many cases they are the only information many health care providers—particularly those being targeted by the company—receive about cancer genetics. This means that patients who might meet criteria for other hereditary syndromes (for which Myriad does not test) are not always receiving comprehensive or accurate information because their health care providers are not genetics experts and are unaware of these other syndromes. By encouraging health care providers with limited genetics expertise to provide “in-house counseling” and order testing, it is our opinion that Myriad is establishing a minimum competency for providing genetic information to patients which falls below published national expert guidelines. The lab is establishing a body of health care providers who, rather than practicing medical genetics, are trained to market BRCA testing for the company that manufactures the test. They have also begun to train a body of patients who have undergone genetic testing to act as “patient advocates” to speak out in favor of genetic testing on Myriad’s behalf. Unchecked and unregulated, Myriad has unrestricted access to providing consumers both directly and through their health care providers with unbalanced, biased information about genetic testing for hereditary cancers.

We have heard from health care providers untrained in genetics who have admitted that they have consulted with Myriad staff when determining appropriateness of genetic testing rather than consulting with a genetics expert unaffiliated with the lab, and rather than referring the patient. We feel that this is a clear conflict-of-interest: consulting with a company employee is not the same as referring a patient to a specialist not affiliated with or employed by a lab with a financial incentive for selling tests. This is another way the genetic counseling process that is a national standard-of-care is being bypassed.

Following up on prior testimony, we are continuing to hear from people who have been tested without benefit of genetic counseling and receive results from doctors or nurses who have no understanding of the significance of test results. We are also learning of many incorrect or inappropriate tests ordered at significant expense to the consumer and/or their insurance company. In some cases tests are being ordered without insurance company pre-approval and individuals learn they do not meet insurance criteria only after they have already paid for testing.

Since no regulatory body monitors or regulates the marketing of tests through CLIA-approved labs, and no entity documents reports of adverse events, we have no way of knowing just how many people are harmed every day by inappropriate genetic testing. Standard medical practice calls for a referral to a specialist when specific expertise is required. Most physicians know to refer someone with a heart murmur to a cardiologist, for example, and to send a patient with a corneal laceration to an ophthalmologist. Despite published guidelines that outline genetic counseling prior to BRCA testing as standard-of-care, because much of the general population is unaware of the existence of genetics experts, and health care providers are being discouraged from referring patients, consumers have no way of knowing that they are receiving substandard care and have no venue for registering complaints.

We urge the Secretary’s Advisory Committee on Genetics, Health and Society to recommend federal action to monitor, regulate, and track adverse events resulting from marketing by laboratories to both consumers and health care professionals, and to require doctors to know about, inform patients about, and refer patients or provide them access to standard-of-care genetic counseling prior to ordering genetic testing for a patient. Thank you.

Since our testimony, we have heard from an FDA representative encouraging the reporting of cases where genetic testing without prior genetic counseling led to emotional or physical harm.  These cases can be submitted through the FDA’s MedWatch online reporting portal.  Consumers, advocacy groups, and health care providers are encouraged to submit these cases to the FDA.  Health care providers and advocates submitting reports on a patient’s behalf should use initials or a first name only to assure HIPAA compliance and/or patient privacy.   FORCE will submit cases on behalf of consumers who wish to file a report but wish to remain anonymous.  Please contact us at: info@facingourrisk.org and put MedWatch in the subject heading.

Comments Submitted to the Secretary’s Advisory Committee on Genetics Health and Society

Yesterday I had the honor of being asked to submit public commentary to the Secretary’s Advisory Committee on Genetics Health and Society.  This committee reports to the Secretary of Health and tackles the emerging and challenging issues being faced as genetic research expands at a rapid pace.  The committee seemed very interested in my statement and members of the committee had positive comments about FORCE and the role we play as an organization advocating for people and families affected by hereditary cancer.  Unfortunately even with a growing number of genetic tests becoming available, there are large regulatory gaps that allow tests that have not be validated to be marketed to consumers without any governing agency overseeing the information being transmitted to consumers.  This is very different from the situation with pharmaceutical agents where the FDA has a role not only in determining what medications are available, but also in overseeing what manufacturers can say about their products, how they are marketed, and in tracking adverse events caused by the product.

Below is a summary of the comments I presented.

 

“I thank the Secretary’s Advisory Committee on Genetics, Health, and Society for inviting me to present comments.  I’m founder and Executive Director of the national nonprofit organization Facing Our Risk of Cancer Empowered (FORCE), an organization devoted to improving the lives of individuals and families affected by hereditary breast and ovarian cancer.  Part of our mission includes advocating for the health and wellbeing of our community affected by these cancers. The goal of my testimony is to alert the SACGHS of a growing issue regarding genetic testing that seems to be increasing in frequency and is taking a toll on the community that I serve and to remind you that people are making real-life decisions based on genetic test results.

 

Unfortunately, once a test is offered to the public, consumers assume and expect that the test has been validated, has gone through an FDA approval process, has clinical utility, and any marketing claims must be true.  The lack of government oversight on laboratory tests by CLIA-approved laboratories is leaving a large knowledge and regulatory gap that is being filled in by parties not necessarily acting in the best interest of consumers.  Lack of government oversight with regards to appropriate genetic testing and assuring access to genetics experts:

• Leads to wasted healthcare spending as inappropriate tests are ordered and improperly interpreted
• Leads to consumer harm as people are being given inappropriate or incorrect information about the meaning of a genetic test results
• Denies consumers information about standards-of-care and denies them the ability to report adverse events or circumstances

At FORCE we have begun to document adverse outcomes in cases where people were not given access to, nor made aware of the option of consulting with an expert in cancer genetics prior to testing. This includes cases where people were told their tests were negative when they were positive, positive genetic tests being disclosed to people while driving, full-sequencing genetic testing being ordered when a single-site test was appropriate, and a recent case where the wrong test was ordered leading a woman to believe she was BRCA negative, when she was actually BRCA positive. This particular woman chose a lumpectomy and radiation over mastectomy based on the negative test result. 

An alarming (but perhaps easily remedied) aspect of the situation is that the above situations can be linked back to actions and communications from the companies doing the testing:

• At more than one conference I listened as genetic testing company exhibitors presented to health care professionals that “you don’t need to refer a patient to a genetics expert first.  You can order the test and if they positive you can then refer them if they want.”
• At a professional society meeting for oncology nurses about genetic testing in physicians’ offices (which was sponsored and entirely moderated and organized by a genetics lab) one panelist held up an educational piece prepared by the sponsor and stated, “This is all you need to begin genetic testing in your practice.”  That particular piece only discussed the genetic tests that were offered by that lab and had no discussion on other genetic tests or hereditary conditions which might have been equally or even more appropriate for patients.
• Recently I participated in a panel and listened in shock as one panel member representing a DTC genetic testing portal boasted of how her company gives patients access to genetic tests that were not recommended by their physician and which they provide outside of standard-of-care recommendations.  It is unclear how a physician could interpret the off-label use of a test they didn’t think was medically necessary and how the patient might use such results to make medical decisions absent of any clear guidelines or supportive research. 
• At the same panel discussion on direct-to-consumer testing, one genetics expert in the audience likened this scenario to the proverbial “fox guarding the henhouse.” 

Government intervention and implementation of the following will help alleviate the problem:

• More oversight of, and at least one agency with jurisdiction over genetic tests and how they are marketed to consumers and physicians.  Consumer stakeholder input should be included if possible.
• Consumers need to know about and be given access to trained experts in genetics, and any published standard-of-care guidelines if available on the genetic condition in question. It should not be up to the laboratory to determine who is or is not competent to order and interpret genetic tests
• Laboratories need to be held accountable for their marketing materials for consumers and physicians with regards to genetic tests
• We need an agency to track adverse events with regards to genetic tests

It should not be up to the test developers to govern themselves or determine the appropriate amount of information, nor to designate the minimal competency for conveying this information.

Thank you for your time and attention.”