Regulating the Next Generation of Genetic Tests

Gene sequencing – also known as genetic testing – is the process scientists use to analyze DNA in search of mutations and variations in an effort to discover more about the connection between genes and traits, health and disease. Since the discovery of BRCA 1 in 1994, the sequencing of genes to find mutations has held importance for people with cancer in their family. With advances in biomedical technology, scientists have developed ways to process thousand of genes at the same time (in parallel) and at lower cost than earlier sequencing methods. These next-generation – or “next-gen” – sequencing (NGS) methods have brought opportunities and challenges to the field of genetics. NGS has allowed the development of panel tests that can look for mutations in many genes, including newly identified genes that might increase cancer risk. One of the challenges involves developing regulations to ensure that the resulting information is of maximum benefit to consumers. Recently, the FDA conducted a forum seeking public input about how these tests might be regulated. FORCE attended and testified on this topic.

Benefits and Challenges of NGS: Genetic tests for cancer-causing gene mutations allow people to better understand their risk for cancer, and take appropriate proactive steps against the disease. The test for BRCA mutations was the first commercially available test to help people make informed decisions about cancer prevention. Now, 20 years later, research indicates that knowing one’s BRCA status and taking risk-reducing steps can help people with mutations live longer. Experts use this information to help people make informed health care decisions to manage their cancer risk. But genetics is not an exact science, and even after two decades of research, and there are still health outcomes associated with living with a BRCA mutation that remain unknown.

We know even less about many of the genes included in NGS panel tests. These panel tests are being offered to consumers to help them assess personal cancer risk, but not nearly enough research has been conducted to identify specific risks and outcomes associated with mutations in some genes in these panels, and even less research is available concerning the best ways to manage cancer risk in individuals who have mutations in these genes.

Oversight of Laboratories That Conduct Diagnostic Tests: The federal government has regulatory standards for clinical laboratories to assure the quality of the labs and the tests they perform. But, these government agencies do not regulate other aspects of genetic testing such as:

  • Whether the tests have clinical utility
    Genetic tests for cancer risk are most useful if results can guide decision-making and most people assume that a test that is commercially available must have value for decision-making. But not all gene changes included in some NGS panel tests have been consistently linked to increased cancer risk. Some gene mutations increase risk, but not enough to change recommendations for risk management. Some genes are not associated with a specific cancer syndrome but still may increase an individual’s risk of some cancers. Currently tests that are run at certified laboratories are not required to meet any standard for clinical usefulness.
  • How the labs interpret and report variant results
    Panel testing returns a high incidence of genes that show a variant of uncertain significance (VUS) – a genetic variation for which the affect on risk of developing cancer is not completely understood. Such results make it exceedingly difficult for experts to advise patients about effective risk-management strategies and to identify family members who should consider genetic testing. Incorrect interpretation of VUS results in BRCA has led to adverse events in some patients, and with the growth of next-gen sequencing, in which VUS rates for some genes may exceed 50%, the incidence of adverse events seems likely to increase.
  • How the laboratories market these tests to doctors and consumers
    People are making medical decisions today based on panel test results, sometimes in the absence of evidence. Therefore, the information that labs provide about these tests, and how they market them to doctors and consumers are significant matters. FORCE was one of the first advocacy organizations to support government oversight of genetic test marketing. In 2009, we provided testimony to the Secretary of Health’s Advisory Committee on this topic, and based on that testimony, the FDA implemented a mechanism for health care providers to report adverse events stemming from laboratory tests.

The full potential of predictive testing can be realized only if patients receive credible and current information that helps them make fully informed decisions. Toward that end, FORCE recently testified that regulatory oversight of genetic testing laboratories ensures that:

  • Patients have access to trained genetics experts who are fully independent of testing labs and can provide them with standard-of-care genetic counseling for all the hereditary syndromes for which they may be at risk – both before and after genetic testing.
  • Individuals performing genetic counseling and interpreting test results meet minimum certification and continuing education requirements.
  • Genetic counselors receive appropriate recognition as health care practitioners by all payers, including Medicare.
  • Patients at increased risk for cancer can access services proven to reduce risk and improve survival or health outcomes—including breast MRI and prophylactic oophorectomy.
  • Resources are allocated to coordinate policies between the United States Preventive Services Task Force (USPSTF), Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA), payers, and other agencies.
  • The legal provisions of Genetic Information and Non-discrimination Act (GINA) and the Patient Protection and Affordable Care Act (PPACA) are vigilantly enforced, and expanded protections for life, disability and long-term care insurance are considered.
  • A process for reporting adverse events associated with NGS – including misinterpretation of test results – is in place and accessible to patients.
  • All laboratories contribute variant data to the publicly accessible database known as ClinVar, and quality control and oversight procedures are created for this public archive that collects information about genomic variation and its relationship to human health.

We will continue to be involved in this dialogue with the regulatory agencies to assure that the best overall health outcomes of consumers remains a priority, and will continue to update you as this topic evolves.

In the meantime FORCE is a resource for all people and families affected by or at increased risk for hereditary breast, ovarian, and related cancers. We are actively building our ABOUT Network Research Registry to study long-term health outcomes for people affected by HBOC and help improve guidelines for medical decision-making.Our registry and our FORCE programs help people who have tested positive for mutations in BRCA, PALB2, PTEN, and other genes linked to cancer, people who have a family history of cancer, those who received inconclusive test results, and those who have not had genetic testing but are concerned about their cancer risk.

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Guest Blog: Join FORCEs at our 2015 HBOC Conference!

by guest blogger, Jane E. Herman

May Goren PhotographyWhen I boarded the flight for my first trip to Orlando in June 2011, my goal was not to hug Mickey Mouse or visit Cinderella’s Castle. Rather, my destination was the sixth annual Joining FORCEs Conference. Not knowing anyone who would be in attendance, I was – not unexpectedly – equal parts nervous and excited.


Me and my mom.

During the course of the previous year, I’d lost my mom to breast cancer, tested positive for a BRCA2 gene mutation, and had a laparoscopic hysterectomy. Four weeks after the conference, I was scheduled for a prophylactic bilateral mastectomy and immediate reconstruction using my own abdominal tissue, which would be micro-surgically reconnected to create new breasts.

The only known mutation carrier in my family at the time, I had met a few BRCA sisters at meetings of New York City’s FORCE group, but I was hungry for more – more medical information, more quality-of-life tidbits, and, perhaps most of all, more (and deeper) connections with others who “get it.” I couldn’t wait to talk to people about my experiences – and learn about theirs – without having to start the conversation by explaining what a BRCA mutation is and how drastically it increased my lifetime risk of breast and ovarian cancer.

From the minute I climbed aboard the shuttle, I got exactly what I needed. Before we’d even left the airport, several fellow riders and I had already connected, sharing details of our BRCA and HBOC journeys for much of the trip to the hotel.

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I came alone to my first conference but soon bonded with kindred spirits.

The next two and a half days flew by in a kaleidoscope of attending large and small group sessions, networking, taking notes, sharing stories, swapping email addresses, strolling through the exhibit area (and making a purchase or two!), attending the ever-popular “show and tell” (for women only, of course), asking questions, and chatting one-on-one with doctors, genetics professionals, and many of the hundreds of BRCA sisters (and a few brothers) who joined me at the conference.

There were a few tears as well, especially when I talked with mother/daughter pairs traveling the BRCA road side-by-side. How I envied their togetherness, and, oh, how I longed for my own mother and for her to know about this thing that we shared. For every tear, however, there were a hundred hugs – and I don’t mean “air hugs.” I mean real, honest to goodness (if you’ll pardon the expression) boob-crushing hugs.

When I returned to Orlando in October 2012 for the seventh annual Joining FORCEs Conference, the hugs began as soon as I entered the hotel lobby.


Dave Bushman provides helpful genealogy tips.


Words cannot begin to express my joy at seeing in person the friends with whom I’d been emailing, texting, and Facebooking for the last year. As in 2011, the days flew by in a whirlwind that was both the same and different from the previous gathering. Presentations by researchers and clinicians brought us up-to-date on the latest developments in a field that moves at lightning speed, while the exhibit hall, once again, offered fun jewelry, pretty scarves, useful products, and connections to an array of organizations whose work benefits members of the HBOC community. Perhaps most significant for me was that with my own mastectomy in the rearview mirror, I was able to “pay it forward” as a “show-er” during “show and tell,” proud of what I’d done and more than willing to share my experience – the good and the not-so-good – with those who were standing where I’d been just one year earlier.

May Goren Photography

FORCE volunteers bonding at 2014 conference

By June 2014, when the eighth annual Joining FORCEs Conference was held in Philadelphia (in partnership with the Basser Research Center for BRCA), I’d been an Outreach Coordinator for New York City FORCE for 18 months. My co-facilitator Laura and I not only drove together to Philadelphia, but also organized a group dinner at a local restaurant on Friday night so attendees from our NYC group could spend time together. In addition to all the things I’d come to know and love at the FORCE conferences – the large and small group sessions, the exhibit hall, the networking, the sharing, and, most especially, the hugs – this time around, my days also included early morning Outreach Coordinator meetings and several sessions designed specifically for participants in FORCE’s Research Advocate Training (FRAT) program.

Conference logo with tagline jpegNeedless to say, I’m eagerly awaiting this spring’s ninth annual Joining FORCEs Conference in Philadelphia for so many reasons. Registration is open now, and I hope to see you there!

Jane E. Herman
, an Outreach Coordinator in New York City, is the executive writer and editor at the Union for Reform Judaism. She maintains a slice-of-life blog,, where, among other things, she writes often about her experiences as a BRCA2 mutation carrier.


Hereditary Cancer Impact Is More Than Skin Deep

Articles about Angelina Jolie’s revelation that she underwent genetic testing and prophylactic mastectomy with reconstruction often emphasize her as one of the world’s most beautiful women, who is still beautiful after all that she has endured. This message can be reassuring; by going public, Ms. Jolie put a more positive spin on the stigmatizing effect of having a “mutation” and undergoing mastectomy. Single-handedly, she started a public dialog about hereditary breast and ovarian cancer (HBOC) that has raised awareness beyond any that has been previously achieved by media focus. Her story provides hope for those who are just beginning to understand or confront their hereditary cancer risk. These are positive developments.

Media reports on HBOC that focus only on cosmetic outcomes, however, can be a double-edged sword, demonstrating that women can come through mastectomy and remain beautiful, but sometimes setting up unrealistic expectations. Some of these articles trivialize the challenges we face, as though cosmetic outcome is the only factor that matters. While other stories sensationalize the decision for prophylactic surgery as an extreme and shocking step. The complexity of HBOC and the accompanying emotional impact is often unreported.

Media attention notwithstanding, those of us who live with HBOC know that learning about hereditary cancer risk and making medical care decisions to stay healthy are not always easy or straightforward, and outcomes are not always positive. Aided by support, credible information, and skilled caregivers, many of us survive, but not all of us emerge totally unscathed.

Survivors and previvors of hereditary cancer are sometimes pressured to feel grateful for the knowledge of their risk. Most of us do appreciate knowing about our elevated cancer risks, and subsequent opportunities to address these risks. But we have also faced loss and grief due to hereditary cancer. We have known fear, life-changing treatments, side effects, and loss of loved ones who are dear to us. In the 16 years since I learned of my own mutation and then experienced treatment, follow-ups, and surgery, I have been there myself. After undergoing mastectomy, chemotherapy, radiation, and surgical menopause in my thirties, I found very little focus, support, or guidance on issues such as sexuality and body image 16 years ago.

I am one of the lucky ones. After years of research, self-advocacy, trial and error, therapy and passage of time; at age 50 I am in the best physical and emotional shape of my life. But I know that so many others with HBOC struggle with the quality-of-life issues. Even after our best efforts, some of us face extended recoveries, long-term consequences, complications, side effects, or outcomes that are not always what we hoped for. For some women, surgery affects their sexual experience. Others don’t feel comfortable with how they look in or out of clothes. Menopause may have reduced or eliminated their desire for intimacy, or changed their ability to achieve sexual satisfaction. These women often do not regret their surgeries, but they are left with emotional scars as well as physical reminders from the procedures.

Whether we struggle with decision- making, are unhappy with our outcomes, or feel satisfied but are trying to adjust to a “new normal,” all of us have a right to process our experiences and grieve our losses. Acceptance and gratitude are not always immediate or easy to attain. Sometimes we have to work at it. Sometimes we need the guidance of experts. And sometimes we just need the support and understanding of those who have been there before us.

In our 2012 survey (unpublished) on long-term follow-up care and medical issues for survivors and previvors, 77% of 900 respondents indicated that they were “somewhat concerned” or “very concerned” about libido and sexuality, and 55% indicated that they had ongoing problems with libido or sexuality. Even when distinguishing responses from survivors and previvors, although more survivors (62%) experienced problems with sexuality and libido, a high percentage of previvors (48%) did as well. These numbers are unacceptable and speak to an unmet need among our community.

Fortunately, organizations like Livestrong are focusing on long-term issues of survivorship. Earlier this year, the National Comprehensive Cancer Network (NCCN), which establishes consensus guidelines for standard-of-care practice in cancer medicine, released its first guidelines on survivorship issues, including sexuality. But clearly, gaps remain in resources and health care services addressing these concerns, for both survivors and previvors.

FORCE programs are also designed to provide this support and guidance. For those who have difficulties accepting their bodies and changes in sexuality from treatment, mastectomy, reconstruction, or surgical menopause, our upcoming free webinar on body image and sexuality may help. Sharon Bober, PhD, Director of the Sexual Health Program in Department of Psychosocial Oncology and Palliative Care at the Dana-Farber Cancer Institute, will explain how women can manage the after-effects of these mind- and body-altering interventions.

Until more attention is given to the complex nature of HBOC and the long-term consequences of our choices, public perception of the HBOC experience will be limited to what is presented by the media. Sexuality and intimacy is a personal and private topic, making it challenging to discuss with health care providers. But if we don’t bring the subject up, most doctors won’t ask us about it. We must continue to advocate for ourselves in order to improve our long-term physical and emotional wellbeing. The health care community needs to pay attention to these concerns and invest in more resources and research on sexuality and intimacy for survivors and previvors as important quality-of-life outcomes. Every woman facing HBOC, regardless of her situation and choices, has a right to feel desirable, emotionally fulfilled, and beautiful inside and out.

Increased Awareness Leads to Accelerated Research

About a million people in the United States carry a BRCA mutation; less than 10% of them are aware of their elevated cancer threat. Recent media coverage of Angelina Jolie’s BRCA status and risk-reducing double mastectomy has brought unprecedented attention to these issues. These reports will narrow the awareness gap while erasing stigmas that are associated with inherited mutations and mastectomy.

One topic that has not been highlighted, described or even discussed is what this publicity could do for hereditary cancer research and clinical trials. Despite all this attention, many people have been quick to point out that BRCA mutations are not common in the general population, and the majority of breast and ovarian cancers are not hereditary. Most cancer clinical trials focus on women with average risk or sporadic cancer; only a handful of research studies are specifically designed for people with BRCA mutations or other inherited cancer syndromes. Recruiting enough qualified research participants – especially for clinical studies that focus on smaller populations – is a critical research challenge. But it is a crucial priority, because clinical trials are required to advance medical care.

As an advocate, I have witnessed the difference that research can make for specific populations. Just 15 years ago, the outlook was bleak for women who developed aggressive breast cancers that overexpress the Her2neu protein. These cancers were known to be aggressive, with high rates of recurrence and mortality. But researchers recognized that some features of these tumors made them vulnerable to therapies that  targeted the Her2neu protein. This led to the development of a targeted therapy known as Herceptin, which received FDA approval in 1998 and revolutionized treatment for women with this type of breast cancer. Herceptin paved the way for development of several newer targeted drugs to treat these tumors. Today, many more women diagnosed with Her2neu positive breast tumors survive their cancer and never develop a recurrence. We can learn from the story of Herceptin (which has been chronicled in books and movies); the role that advocacy and awareness played in its development, and the challenges that had to be surmounted for eventual FDA approval of the life-saving drug.

That is precisely the type of focused effort (and results) we need for hereditary cancers, which tend to act more aggressively than other cancers, and to occur at a younger age. There are special features in the cancers of people with BRCA mutations that open up opportunities to develop new and better agents. Right now, we are teetering on the cusp of exciting research that could revolutionize treatment and prevention of hereditary cancers. PARP inhibitors, for example, are medications that were specifically designed to combat BRCA-associated cancers. Clinical trials are open and enrolling participants to determine if these agents improve survival in people with mutations. For example, the BROCADE Study is a large, phase II PARP inhibitor study enrolling people with advanced, BRCA-associated breast cancer. Large studies enrolling mutation carriers with ovarian cancer will be opening soon.

As PARP inhibitor research progresses, newer agents are also being studied to see if they may work particularly well for hereditary cancers. At the recent American Association of Cancer Research (AACR) meeting, results were presented on a combination of sapacitabine and seliciclib, two new drugs that may work particularly well for BRCA-associated cancers. Another new agent called PM01183 is in early clinical trials for people with advanced, BRCA-associated breast cancer. Might these new drugs hold the key to improved survival and better quality-of-life? Could PARP inhibitors or newer agents revolutionize treatment for hereditary cancers, and turn out to be our community’s Herceptin? These studies fill me with hope! But the only way to know is through clinical trial research, which requires recruiting a sufficient number of volunteers.

The most significant hurdle facing us is completing these research studies so that we can prove whether or not these new drugs work. Last year, a major study on hereditary ovarian and fallopian tube prevention and detection closed due in part to lack of participants. The study closure was a tragic loss for our community; and more so, could send an unfortunate and untrue message to researchers and funding agencies that the BRCA population is too small and too hard to recruit. While we continue to fight hard to get more hereditary cancer research funded, we must also devote resources to raising awareness and spreading the word about current research opportunities open to people with BRCA mutations or hereditary cancer.

One huge benefit of celebrities coming forward with their stories is that more people are motivated to learn about their inherited risk, and consider genetic counseling and testing. Our community will continue to grow as more people learn they carry an inherited mutation. FORCE will continue to lead the way; uniting all people facing hereditary cancer and providing support, education, and access to the latest research studies. Progress may feel slow and incremental, but an increasing attention to hereditary cancer may be just what we need to propel research and outcomes to the next level.

For more information on participating in hereditary cancer research, visit our website’s Clinical Trials and Research section. Over the next few weeks we will be updating the prevention, detection, and treatment studies section of our website, so stop back frequently. Our next Be Empowered webinar on PARP inhibitor research will be held June 27.

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.

The Cavalry Has Arrived!

When I founded FORCE in 1999 it was in the early days of BRCA discovery and testing. I had my own BRCA testing in 1998, over a year after my diagnosis with breast cancer, and only after learning about hereditary cancer by reading a magazine article about BRCA. I immediately understood the significance and power of identifying people with genetic predisposition to cancer, with the goal of preventing cancer or detecting it early. But the technology was met with suspicion and alarm by many individuals and groups, even in the face of emerging research that documented the value of identifying those with a BRCA mutation.

I spent a good portion of FORCE’s early years explaining why our community was important. Back then the hereditary cancer community was frequently dismissed or minimized, emphasizing the fact that we were a small subset of a larger whole. Granted, we don’t represent a majority of the cancer community, but we shoulder a disproportionate cancer burden. And because of our extraordinary high risk for cancer and the generational aspects of inherited cancers, HBOC individuals and families are an overburdened and under-resourced community. We require unique research and resources that provide information and evidence-based solutions for the extraordinary issues we face.

We worked hard in those formative years to raise awareness, unite our community, and assure that both survivors and previvors were acknowledged as cancer stakeholders who had a say and a place at the table. We fought for awareness, educated people on the differences between hereditary and sporadic cancer, advocated for better early detection and risk-reduction options, and helped people make informed decisions. Along the way, we were often asked to justify the prophylactic options for risk-management, and even the need for a hereditary cancer advocacy group like FORCE.

As awareness has grown, FORCE has grown, and so has our voice in the cancer community. And yet there are still many areas of unmet needs when it comes to hereditary cancer clinical care and research. Although improvements have been made, current options for prevention, detection, and treatment of hereditary cancer are still inadequate. Too many people are being diagnosed with and succumbing to hereditary cancers, and the path to drug development and FDA approval for example for PARP inhibitors has been glacially slow. After14 years of passionate advocacy and incremental and modest gains, it would be easy to be discouraged. But as many of you know if you read my blogs, I also like to focus on achievements and advancements, and there have been many.

Once in a while, I have had the privilege to witness a landmark event, a game-changer for our community. Last Monday night was such an event. I was honored to be among over 200 people who attended the opening of the new Basser Research Center for BRCA within the Abramson Cancer Center of the University of Pennsylvania. Established through a transformative philanthropic gift from Mindy and Jon Gray, the center is dedicated to the memory of Mindy’s sister, Faith Basser, who succumbed to hereditary ovarian cancer. The center is devoted solely to research and provision of care relevant to BRCA1 and BRCA2. Not a dry eye could be seen as we watched a video that included Faith’s story and how she became the motivation for her family’s endowment. The video also included stories of members of our community, who shared the devastating toll of hereditary cancer on their families. That night, all of us who attended and watched the video, listened to the speakers, and met the Basser Research team understood the center’s clear, overarching message: HOPE. I was witnessing history being made and a new era for the HBOC community.

I was honored to be among over 200 people who attended the opening of the new Basser Research Center for BRCA

Certainly our community will continue to face challenges, hardship, disparity, and unmet needs. But we have champions and a path to a brighter and more optimistic future with the establishment of the first research center dedicated to the pursuit of better detection, prevention, treatment, survivorship, and supportive care for HBOC. As I told Jon and Mindy Gray when I thanked them for this amazing gift to our community, “the cavalry has arrived.”

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.

The Lights of May

We were late.  The last hint of twilight faded and although we were close to home, I was nervous.  It was already 9:30, way past Beau’s bedtime, and instead of being snug in bed we were still two blocks from home. By that time I was almost running, hurrying my son when he stopped.

“Mommy, what was that?”  he pointed to a neighbor’s yard.
“C’mon Beau, we’re late,” I pleaded but he wouldn’t budge.
“No, Mommy, what is that?” he insisted, “It’s green!”

At 5 years old, Beau was in the habit of pointing out every pebble, plant, and piece of litter and dirt along the way. A walk around the block with him could turn into an hourlong adventure.  But tonight we had already walked a couple of miles to the store and back; I was tired and still had work to do. Our sleepy Florida neighborhood was generally safe, but it was still a source of anxiety for me after dark.

I was anxious a lot. And certainly I wasn’t as patient as I used to be. Putting off parenting as I pursued my veterinary career, I was 31 when Beau was born. But it seemed I had waited too long to have the family I had dreamed of when I was diagnosed two years later with breast cancer. Before my diagnosis, I was at the peak of my veterinary career.  My health had never been better, and I no reason to think my life would be forever changed by a cancer diagnosis. I had no advance warning that I had inherited a BRCA mutation and was at such high risk. My diagnosis was followed by two years of dealing with my cancer, initially with surgeries, then—when my cancer recurred—more treatment that included chemotherapy, and radiation. On May 15, 1998, after learning of my BRCA 2 mutation, I underwent a risk-reducing oophorectomy and hysterectomy at 35, abruptly ending my plan to have more children. A prophylactic mastectomy and reconstruction on my other breast followed. During treatment for the recurrence, my family relocated to Houston. All I could think about there was the time when I would finally be done and could reclaim my previous life and career.

Yet when I finished treatment and returned home, fear of another recurrence was my constant companion. It consumed almost every waking moment, sometimes leaving me frenzied to achieve all I hoped to do in a compressed moment of time. Trying to balance my veterinary career with my new role running FORCE, (back then a very new and small nonprofit organization), and still be there for my son and husband while battling constant anxiety was taking its toll. I was struggling to keep my head above water professionally and personally, and failing. Two years since returning home to Florida, after all the treatments and prophylactic steps I had taken to survive, I wasn’t really living. And my husband and son, the two people who needed me the most, shouldered much of the collateral damage from my unhappiness.

Tonight walking with Beau seemed no different. As I tried to hurry my son, I was oblivious to his world. I grabbed his hand and pulled him along.

“Beau, it’s probably just a piece of garbage!”

“Mommy it’s a green light!”  he insisted.  “YOU HAVE TO STOP!”  Beau didn’t often defy me, and his insistence took my by surprise. There were so many things pressing down on me; yet, for one moment I considered what my son was saying. For the first time in a while I thought about things from his perspective. I took a breath and I stopped with him.

“I don’t see anything.”
“There it is again!”

I studied the darkness of our neighbor’s yard for a glimpse of Beau’s mysterious light.  There. And there. What had been invisible a moment ago was suddenly revealed. A firefly, several, actually. Bright green flashes, blinking intermittently in the dark.

I was amazed. “I don’t believe it Beau, those are fireflies!”  I told him about the fireflies in New York when I was a child. During my 11 years living in Florida never once had I seen a firefly here. The hurry for bedtime and my weariness now forgotten, we watched Nature’s lightshow together for the next 30 minutes.

The following evening we could hardly wait for dark. It didn’t take long for the show to begin. We chased after the flying lights, then caught one and studied it.  It flashed and tickled in our hands.This firefly was different than others I had seen; the light came from its head. A beetle with glowing eyes!  Later, the Internet informed us our flying friend was Pyrophorus, the only bioluminescent click beetle.

We chased the fireflies for the next few weeks, even relocating some to our own yard. I spent many happy moments reconnecting and sharing joyful times with Beau. How long it had been since I had felt that. That spring, along with the flowers and the fireflies, hope and happiness were emerging; emotions that I had suppressed since my recurrence. From then on, every May, watching for the fireflies became a sacred ritual shared between Beau and I.

Pyrophorus – Photo by Adrian Tween

Sometimes it’s the small moments that emerge from the large and scary events in life to define us. That night, seeing the world from my small son’s perspective opened me up to the joy and wonder I had been missing. Sometimes a tiny dose of joy reminds us how attainable it can be. Since my oophorectomy, May had been a time of grief for me. That spring night restored many gifts that cancer had taken and helped me to recapture and hold on to the connections that had made all my treatments worthwhile.

Several years later, I gave up my veterinary career to dedicate more attention to FORCE and my family. I still think of that night as a pivotal moment when I was reminded what was really important. I still get stressed and anxious and I still sometimes feel there is not enough time to accomplish all that I hope to in life. But I have gained more perspective-more ability to see the world through the eyes of a child.

Although I have heard the glowing beetles can be found here in Tampa, where we moved eight years ago, I have yet to see them. But it is May, and I haven’t looked for over a year. Tonight I will make time to see if I can find one.