Cancer Genetic Testing Should Be Performed in the Health Care Setting

by Lisa Schlager

There is a flood of information available about genetic tests for cancer risk in the media, and even at community events, such as health fairs and senior centers. If these promotions have caught your attention and you are considering testing, there is important information that you should know first.

Facing Our Risk of Cancer Empowered (FORCE) is a national nonprofit organization that provides resources to help people make informed decisions about genetic testing for cancer risk. National standard-of-care guidelines recommend genetic counseling with a qualified expert before and after genetic testing. FORCE agrees that talking to a health care provider with expertise in cancer genetics pre- and post-genetic testing is important. This helps assure that:

  • The right test is performed (there are many available) at a reliable, high-quality lab.
  • Your results are interpreted correctly.
  • You receive accurate information about what the results mean and your medical options.

When genetic testing for cancer risk is conducted outside of a health care setting—as described below—the likelihood of misinformation is high, which could lead to harm.

Tests Sold in Non-Health Care Settings

Members of our community have reported sales representatives aggressively promoting genetic tests directly to consumers at health fairs, senior living facilities, on Facebook, and in other non-medical settings. These sales representatives have been evasive about the actual lab performing the testing and have provided misleading information, making false promises of “free” genetic testing to people who don’t qualify and billing insurance companies or Medicare for tests which may not be medically necessary.

BRCA Testing Through 23andMe

In March 2018, the FDA approved marketing of 23andMe’s test for the three BRCA mutations most commonly found in people of Ashkenazi Jewish ancestry. Over 6,000 different mutations—in BRCA1, BRCA2 and other genes—are associated with an increased risk of cancer. The 23andMe BRCA test only looks for three of these many mutations (two in BRCA1 and one in BRCA2). This extremely limited test may provide people with a misleading understanding of their cancer risk. (in 2018, FORCE released a public statement to educate people about the limitations and drawbacks of this test.)

The FDA label warns people not to use the 23andMe BRCA test results to make medical decisions, and advises individuals to have a confirmatory test with a clinically certified lab to assure accuracy of the results. The agency also emphasizes “it is important for patients to consult their health care professional who can help them understand…their individual cancer risk.”

Using Ancestry Testing Data to Calculate Cancer Risk

Many companies (Ancestry, MyHeritage, 23andMe, etc.) offer genetic testing to help people locate relatives or learn more about their ethnicity. These tests are intended for recreational purposes and not meant to guide medical decision-making. Some third-party online programs (Promethease or Livewello, for example) allow people to submit their ancestry test results to discover additional information about their risk for cancer and other diseases. Ancestry tests, however, often do not produce comprehensive, high-quality DNA data.

FORCE has received numerous reports of people receiving incorrect information about their cancer risk after running DNA results through a third-party tool. A study published in 2018 revealed a high number of false positives in this type of information; as a result, people incorrectly thought they had a genetic mutation that increased their risk for cancer, which they do not have.

Further, it is impossible to know how many people receive false negative results, leading them to believe that they do not have a predisposition to a disease such as cancer when, in fact, they do have a mutation that increases their risk.

Genetic Testing is Regulated

You have a right to know the name of the lab performing your genetic testing. Beware of
representatives selling genetic tests for unnamed labs. Genetic tests are currently regulated by the FDA and CLIA. When ordering lab work such as a genetic test, health care providers typically order them through a trusted, CLIA-certified lab, which is regularly evaluated for quality assurance. The FDA aims to ensure that test marketing materials and claims are accurate, and that they address the information needs of the approved audience—health care providers or the public. If you have concerns or a complaint about a laboratory, you or your health care provider can file a complaint with CLIA and/or the FDA.

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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HBOC, FORCE, and the President’s Precision Medicine Initiative

pmilogoRecently, President Obama outlined his Precision Medicine Initiative, which generated a lot of buzz. If successful, the plan will move medical research toward personalized treatment options that are based on people’s genetics, environment, lifestyle, and individual preferences. I’m excited that the White House is recognizing and committing funding towards an approach to health care research that FORCE has been endorsing for 16 years. Since 1999, FORCE has been a leader in promoting personalized medicine research, and increasing access to advances resulting from this research. We’ve helped thousands of people make informed healthcare decisions surrounding hereditary cancer risk, prevention, detection, and treatment. We will offer our expertise and lessons learned over the past 16 years to assist the National Institutes of Health and other government agencies in the implementation of this initiative.

Highlights of the President’s plan, which correspond closely with much of FORCE’s longtime work and our future goals include:

  • Developing new cancer treatments based on genetic information
    Experts know that hereditary cancers develop and behave differently than sporadic cancers; they use this knowledge to develop new approaches to preventing and treating these cancers. FORCE has championed research of PARP inhibitors and other novel approaches against HBOC-related cancers. We continue to mobilize

    Lisa Schlager VP of Policy at FORCE testifies to the FDA in favor of Lynparza approval.

    FORCE VP, Lisa Schlager, testifies to FDA in favor of Lynparza approval.

    patients to enroll in clinical trials, and urge the FDA to facilitate development and approval of new therapies to fight hereditary cancers. This past December, our efforts were rewarded: the FDA approved Lynparza (olaparib), a PARP inhibitor therapy, to treat advanced hereditary ovarian cancer caused by BRCA1 or BRCA2 mutation in women who have received prior chemotherapy.

  • Identifying and addressing privacy issues associated with genetic medicine
    FORCE worked as a member of the Coalition for Genetic Fairness throughout its 13-year effort to ensure passage of the Genetic Information Nondiscrimination Act (GINA). Signed into law in 2008, GINA prohibits genetic discrimination in health insurance and employment. Throughout the legislative process, we regularly updated our ginacommunity about the issues, what we were doing, and what our members could do to hasten the passage of GINA. Even after the law was passed, we continued to educate with a survey to assess consumer knowledge about genetic discrimination. In 2009, we presented our findings, which were later published in a scientific journal, at the annual meeting of the American Society of Human Genetics. Our efforts to support GINA continue. We inform consumers about GINA laws, and are currently working on legislative protections against genetic discrimination in life and disability insurance.
  • Working with the FDA to establish a regulatory framework that includes genetic information
    In 2009, FORCE submitted testimony to the Secretary’s Advisory Committee on Genetics Health and Society (SACGHS) objecting to the lack of a regulatory body to monitor certain aspects of genetic testing for consumers and health care providers. We have urged regulators to establish federal oversight of marketing of genetic tests, tracking of adverse events, and monitoring providers’ adherence to pre-testing genetic counseling requirements. As a direct result of our testimony, the FDA implemented a system to track adverse outcomes of testing. In ongoing communications, we encourage the FDA to consider the unique aspects of hereditary cancers in an effort to expedite development and approval of drugs specifically targeted to these diseases.
  • Screen Shot 2015-02-20 at 1.31.21 PMEmpowering patients in the era of personalized medicine
    Following delays of PARP inhibitor research, FORCE mobilized HBOC stakeholders to educate and inform health care providers and consumers to strategically increase enrollment in critical HBOC targeted therapy clinical trials. We continue to empowerindividuals to advocate for themselves and family members, and to participate fully in their healthcare decision making based on their own unique circumstances. FORCE provides straightforward, easy-to-understand material on all aspects of hereditary cancer, and timely medical, scientific, and genetic information from highly trained pi-newsletterexperts. We offer easily accessible peer-to-peer support—both in-person and virtually. FORCE also participates in many alliances; collaborating with academic institutions, other advocacy groups, and industry to facilitate better outcomes for our community members.
  • Creating a million-person, patient-powered research network
    Screen Shot 2015-02-20 at 1.51.34 PMFORCE is making impressive progress towards this goal. Our ABOUT Network is the only patient-powered research network built and governed by and for the HBOC community. One of only 29 networks participating in the development of the National Patient-Centered Clinical Research Network (PCORnet), ABOUT will connect health information and outcomes with the electronic health records of 70 million Americans. This highly innovative database is a government-funded initiative. According to Joe Selby, MD, MPH, Executive Director of the Patient-Centered Outcomes Research Institute, PCORnet will, “harness the power of health data from millions of patients, properly safeguarded, to conduct research more efficiently.” As part of PCORnet, ABOUT is well positioned to participate in the Precision Medicine Initiative. In fact, the Precision Medicine Initiative highlighted stories that demonstrate the power of personalized medicine. FORCE member and patient advocate Melanie Nix, who serves on the ABOUT Network Steering Committee was featured in the Precision Medicine Initiative blog (you can read more about Melanie’s story and why she joined ABOUT in our recent

    Melanie A Nix headshot

    Melanie Nix

    newsletter). To achieve our research goals quickly, ABOUT is seeking to enroll as many Americans as possible into the registry. By collecting real-world health care experiences, our research will drive improvements in the quality of health services; highlight best practices for preventing, diagnosing, and treating hereditary cancer; and ultimately improve future outcomes.

As pioneers and supporters of personalized medicine, FORCE will work hard to assure that this initiative will incentivize research, prioritize global access to quality care, and improve outcomes for people affected by HBOC. Along the way we will engage stakeholders to make sure that our efforts are responsive and representative by:

  • training members of our community to participate in research advocacy through our Screen Shot 2015-02-20 at 1.31.48 PMFRAT program
  • connecting trainees to opportunities where they can represent the HBOC community on research advisory boards and panels.
  • enlisting trained FRAT advocates to participate in our ABOUT Network governance and work groups to help determine how the research will be conducted.
  • using community input to generate unanswered questions needed to make informed medical decisions through our ABOUT Generator And Percolator (GAP) Tools.
  • collaborating with partners that can help us engage people from underrepresented populations.
  • providing members the opportunity to help prioritize research.
  • disseminating research findings to consumers and health care providers.

We look forward to working with our community, policymakers, government agencies, advocates, medical experts, and biotechnology companies to advance the conversation around personalized and precision medicine, while making sure that the interests and concerns of people with HBOC remain at the forefront of this initiative. Stay tuned!

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.

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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.

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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, JanetheWriter.com, where, among other things, she writes often about her experiences as a BRCA2 mutation carrier.

 

Spreading HBOC Advocacy to Japan

Last month I had the honor of giving two talks at a conference organized by the Japanese HBOC Consortium in Tokyo: one for patients and the other for health care providers. Most people in Japan have little input into their health care decisions and do not question their doctors’ recommendations. The conference organizers hoped that my talk might inspire participants to organize an advocacy organization in Japan similar to FORCE to unite toward improving the situation for people with HBOC.

Japanese HBOC Patient Symposium Panel

Panelists from the HBOC Patient-Focused Symposium: (from left to right) Stacy Lewis, YSC; Naomi Sakurai, cancer advocate; Sue Friedman; Chieko Tamura, CGC, genetic counselor; Dr. Shozo Ohsumi, medical oncologist; Dr. Yamauchi, breast surgeon

 

I was joined by friend and colleague, Stacy Lewis, Chief Program Officer at Young Survival Coalition, who was also invited to speak about the important work that YSC is doing for young women with breast cancer. It was an incredible eye-opening experience that helped me appreciate how far we have come in research, clinical care, and resources for the HBOC community in the United States in last 16 years since FORCE was founded.

My talk for the patient community focused on four areas:

  1. Why I became an advocate
    I spoke about my personal health care experiences that led me to take action and start an organization to unite the HBOC community and improve the situation for others: misinformation I received from my health care team, the lack of awareness and support around HBOC, and the absence of research outcomes back in 1999 when I was making my health care decisions. I encouraged the lay audience to learn as much as they could about their health care options and speak out to assure that they are receiving the best care for themselves.
  2. The creation and trajectory of FORCE
    I explained the path from self-advocacy to advocating for others. By publicly sharing my story and seeking other like-minded people, we were able to organize the U.S. HBOC community into a cohesive unit. I shared the growth of FORCE from a small single-staffed nonprofit to a team of 11 employees and over 150 volunteers and the leader in providing programs and resources for the HBOC community. I spoke about the importance of determining touchpoints where we could affect positive change and influence policy, guidelines, and laws to improve the situation for previvors and survivors. I encouraged the audience to explore the ways that they could influence policy and access to care in Japan.
  3. What FORCE is doing in the HBOC world
    I provided highlights on FORCE’s work and programs in 4 key areas: education, support, research, and advocacy.

    • Education is critical for people to make informed decisions. I outlined FORCE’s education programs, including our website, publications, webinars, conference, and our new XRAYS program.
    • FORCE support programs assure that no one faces hereditary cancer alone. Our support programs include our toll-free helpline, our in-person outreach meetings, our message boards, and our new Peer Navigator Program, which will launch this year.
    • HBOC research is the path to better treatment, detection, and prevention options. I discussed the ABOUT Network, the first research registry organized and governed by and for the HBOC community. The audience was interested in the concept of patients setting research priorities and helping to design research studies. I also spoke about how FORCE matches patients to HBOC-specific research through our Research Search Tool and our Featured Research Page.
    • I shared FORCE’s advocacy work, including our efforts to help pass the Genetic Information Nondiscrimination Act (GINA). I described FORCE’s input and testimony regarding national guidelines, gene patenting and direct-to-consumer marketing of genetic testing. I introduced our FRAT program, which trains consumers to weigh in on research and regulatory processes on behalf of our community.
  4. “Take home messages”  
    • One person can make a difference
    • Many people united and working together can make an even bigger difference.
    • It helps to have outspoken champions for the cause. I encouraged the audience to find people in government or the media who had been impacted by hereditary cancer.
    • HBOC research advances and resources developed in one country provide global benefits. There need for HBOC-focused advocates is worldwide; I challenged the audience to look within to see if any of them might carry the advocate torch in Japan.
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I had the opportunity to meet survivors, previvors, and providers who expressed gratitude for the work FORCE is doing.

I encouraged providers who specialize in cancer and genetics to work together with advocates to help them create evidence-based and balanced education materials and programs. I spoke about the importance of educating patients to participate in their health care decisions, and introduced the term “shared decision-making”—an important concept in the US.—meaning that medical decisions are part of a partnership between patients and health care providers. I provided examples from the ABOUT Network, our clinical trials matching and research recruitment efforts, and our FRAT Training program to emphasize why consumers should be invited to participate in and help drive the national HBOC research agenda. At a reception held after the symposium, I had the opportunity to speak one-on-one with Japanese survivors and previvors who expressed gratitude for the work FORCE is doing.

 

Some presentations were translated into English, giving me further understanding of the situation in Japan. The Japanese speakers spoke frequently about how HBOC support and information was better in the United States, and how their goal was to improve the situation in Japan. It was validating to see the term “previvor” used frequently in the presentations – highlighting their interest in incorporating genetic testing and preventive services into the Japanese health care system. I was struck by how much they strive for many things we take for granted. For example, in Japan:

 

  • access to BRCA genetic testing is minimal. Only about 100 patients a year receive genetic testing for which people must pay out-of-pocket.
  • high-risk women have very little access to preventive services such as MRI and prophylactic surgery.
  • no laws protect high-risk people from insurance discrimination, and fear of such discrimination is prevalent.
  • although open clinical trials for PARP inhibitors are recruiting in Japan, the drugs are not approved or available. In contrast, the FDA recently approved Lynparza (olaparib) to treat BRCA-associated ovarian cancer in the U.S.

 

As an advocate, I’m accustomed to pointing out systemic issues needing improvement. I have blogged about these topics in the past, including recommendations to expand the United States Preventive Services Task Force guidelines on genetic testing for cancer to include cancer survivors; men, Lynch and other cancer syndromes, and risk-management options such as MRI and risk-reducing surgery to assure coverage by insurance companies, the negative impact of gene patents, and the need for: more HBOC research, implementation of risk-based screening, and better risk-management options. Uptake of genetic services in the U.S. for people who meet guidelines is still very low, and great disparities in access to care still exist. But listening to the situation faced by our Japanese peers has helped me appreciate the progress we have made in the 16 years since FORCE was founded and has motivated me to do what I can to improve the situation for the global HBOC community.

 

 

Happy New Year, Happy Birthday, Sweet 16!

shutterstock_29561851New Year’s Day is always a nostalgic time for me. Sixteen years ago today, I founded FORCE, not because I made a conscious choice to start a nonprofit organization on New Year’s Day, but because following my recovery from cancer, that day signified the tipping point between my need to rejoin my life-in-progress as a veterinarian and my desire to affect positive change—through more information, research and resource—for the HBOC community.

The last 16 years have not always been easy, especially in the early days of FORCE, when the “organization” had a staff of just one person. Some years, I was already exhausted by New Year’s Eve and I was ready for the year to end. But this year is different. With a staff of 12 and over 120 volunteers, new and exciting initiatives including our ABOUT Network Research Registry (if you haven’t joined yet, please consider it), our newly-launched XRAYS Program, and an incredible win with FDA approval of a new agent for BRCA-associated ovarian cancer, I feel excited and energized for the new year.

I hope that our community feels energized too. In the spirit of shared enthusiasm, here is a list of things that people can do to effect positive change for themselves, for the HBOC community, and for FORCE:

 

A Game-Changing Holiday Gift for People with BRCA Mutations

Today is a landmark for the HBOC community!

After almost a decade of research, AstraZeneca has received FDA approval for Lynparza (also known as olaparib) for women with BRCA mutations who have ovarian, fallopian tube or primary peritoneal cancer, and who responded favorably to their initial treatment. This is the first FDA-approved PARP inhibitor, and it is a great win for the HBOC and BRCA community.

FORCE has been passionately advocating for PARP inhibitor research for the last eight years. At our Joining FORCEs conference in 2009, during our hereditary cancer research plenary, I made a personal vow to our community that FORCE would work tirelessly and do whatever it took to assure that the clinical trials on PARP inhibitors were fully enrolled, that the research was completed, and—if the agents worked—that we would advocate for FDA approval.

Lisa Schlager VP of Policy at FORCE testifies.

Lisa Schlager VP of Policy at FORCE testifies at FDA ODAC meeting.

This past June, we were one of a handful of advocacy organizations to testify at the FDA hearing of the Oncology Drug Advisory Committee (ODAC) in favor of accelerated FDA approval of this agent. Early word from the FDA was that more research was needed before it would approve olaparib.

PARP inhibitors are “targeted therapy” drugs that target tumors based on their specific biology. Developing these “smart” drugs requires a greater understanding of how cancer cells differ from other cells, and identifying cellular vulnerabilities. Targeted therapy uses specific treatments to attack the unique weaknesses of certain cancers based on their cellular genetic traits. PARP inhibitors block an enzyme used by cells to repair damage to their DNA. In people with BRCA mutations, PARP inhibitors may work by keeping cancer cells from repairing themselves once they’ve been damaged by chemotherapy, while sparing healthy cells.

Despite early positive findings, PARP inhibitor research almost came to a halt several years ago due in part to challenges arising from studying drugs that may only benefit small subsets of a larger cancer patient population. Fortunately, due to champions within the scientific, advocacy and biotech communities, the important research continued. FDA approval of Lynparza is the culmination of these ongoing efforts.

There is still much work to be done. Many clinical trials are enrolling cancer patients to pinpoint the best time to start treatment with PARP inhibitors in patients with ovarian cancer; determine whether these agents work equally well for BRCA-associated breast, pancreatic, and other cancers; and identify whether these agents benefit people who do not have BRCA mutations. We still desperately need our community to participate in these ongoing research studies. Still, FDA approval of olaparib for ovarian cancer sends an encouraging message to researchers that we hope will lead to new innovations for more effective detection, prevention and treatment for people with hereditary cancers.

This is an amazing holiday gift and game-changer for all members of our community. Oncologists now have a new weapon for treating hereditary ovarian cancer. This news will likely produce other benefits as well. We will undoubtedly see an increased uptake of genetic counseling and testing among women who are diagnosed with ovarian cancer, and whose treatment may be impacted by whether or not they carry a mutation. Identifying more people with a BRCA mutation will increase the numbers of people who can take part in lifesaving HBOC research. Having more people who are aware of their positive BRCA status will grow our community, increasing members who can advocate for positive change through resources, policy, and research. Finally, identifying more people who have BRCA mutations will raise the profile of hereditary cancer in the public eye.

On a personal note, as a cancer survivor, a person with a BRCA mutation, a relative of other high-risk family members, and a friend of people currently battling advanced hereditary cancer, this news gives me hope and comfort. Yet even as I celebrate with the community, I need to pause and reflect on the many brave and cherished soles for whom this progress did not come soon enough; Sherry Pedersen, Caryn Rosenberg, Linda Pedraza, Jan Finer, Debra Brooks, and too many more to name. You have all touched me in a profound way and inspired me to work harder to accelerate progress in HBOC research.

Finally, I would like to acknowledge all who played a role in this achievement: the scientists who work tirelessly to advance cancer research, the foundations and agencies that direct funding to HBOC research, the biotech companies that invest in greater options for this subset of the larger cancer community, and the brave people who volunteered for PARP inhibitor research studies. From the bottom of my heart…thank you!

 

 

Education, Medical Decisions, and Regret

A recent AARP article that contained an interview with rock stars Sheryl Crow and Melissa Etheridge brought awareness to the individual and personal nature of genetic testing, hereditary breast and ovarian cancer (HBOC), and the medical challenges that accompany inherited breast cancer. The article also led to some heated responses from members of the HBOC community. 

 

The HBOC community has had its share of celebrities. Whenever public figures disclose that they carry a BRCA mutation or have hereditary cancer in the family, it raises the profile and awareness of hereditary cancer. Christina Applegate, Sharon Osbourne, and, most prominently, Angelina Jolie, have all revealed their mutation status. Others, like René Syler, Cynthia Nixon, and Wanda Sykes have shared their family histories, and although they have not tested positive for BRCA, some other familial factor may be causing breast cancer in their families.

It’s difficult enough making medical decisions around HBOC, but celebrities have an added burden of being in the public eye. People look up to them. As individuals in the spotlight share their journeys and decisions, the public assumes they have access to top information and the best doctors. More weight is given to celebrities’ opinions and medical choices than those of the average person, and we often take for granted that celebrities’ statements are accurate.

The AARP interview quoted Ms. Etheridge as saying, “I have the BRCA2 gene but I don’t encourage women to get tested.” Although she doesn’t use the word “regret” it certainly sounds as though she has misgivings about testing. Melissa Etheridge is a member of the HBOC community, and by extension a member of FORCE’s constituency. FORCE empowers people to make informed medical decisions. We validate their feelings, and support people on the HBOC journey. I support Ms. Etheridge’s decisions, but I am saddened to think she has regrets about her choices.

Ms. Etheridge said in the AARP article that her doctor recommended testing, but she never mentions receiving genetic counseling from a qualified expert. I do think this could have changed her perception of genetic testing and highlights the value of receiving comprehensive information on which to base your medical decisions. Information can be the antidote to regret.

In the interview, Ms. Etheridge also says, “Genes can be turned on and off. I turned my gene on with my very poor diet.” FORCE wrote a letter that was co-signed by members of our scientific advisory board and sent to the editor of AARP regarding Ms. Etheridge’s statement. USA Today subsequently published an article about our letter to AARP which included interviews with members of FORCE and the HBOC community who expressed views that differed with Ms. Etheridge. Many members of our community consider the information received from genetic counseling and testing as lifesaving. In FORCE’s letter, we expressed concern that readers may think that BRCA mutations and their effects on cancer risk can be modulated solely with diet to prevent cancer, and conversely that those with mutations who become diagnosed with cancer somehow caused it with a poor diet. Although several studies have shown that eating a healthy diet can lower the risk for certain cancers, these studies have been large-scale general population studies, and the actual protection for a given individual may be small. There are many reasons to eat a varied and healthy diet, including protection from numerous diseases. But not enough evidence suggests that diet and lifestyle alone can protect people from BRCA-associated cancers.

Screen Shot 2014-12-15 at 12.04.41 PMI do want to point out that our letter was directed to the editors at AARP and not Ms. Etheridge, who is entitled to her opinion on testing. Our issue is the lack of context and evidence-based information that surrounded her statements about cancer risk, diet, and genetic testing that could have educated AARP’s readership, and helped readers to make their own informed decisions about whether or not to undergo genetic testing.

I believe that access to a genetics expert and support via FORCE empowers people to make the medical decisions that are right for them. Ms. Etheridge’s example shows that we can do a much better job of educating and supporting people facing hereditary cancer; it highlights the critical need for FORCE to continue our efforts to help people feel empowered and live the healthiest and most fulfilled lives possible.

When HBOC is in the news, it opens a discussion, demystifies inherited cancer, and removes the stigma associated with words like cancer, mutation, and mastectomy. Medically inaccurate information about cancer, genetics, and HBOC, however, is abundant in the media and harmful to consumers. This is why FORCE is launching our XRAYS (eXamining the Relevance of 

???Articles for Young Survivors) program, which is supported by a grant from the Centers for Disease Control. The funding comes from passage of the EARLY Act, legislation that was first introduced to Congress by Representative Wasserman Schultz, who also carries a BRCA mutation, and is up for congressional renewal. The EARLY Act funds programs by organizations that focus on young women and breast cancer. FORCE’s XRAYS Program will allow us to critically review articles in the media, correct any inaccuracies, and write a lay level summaries of the research or information presented. The reviews will be accompanied by an “at-a-glance” graphic representation for readers to easily determine if they should read and believe the article and what relevance it may hold for their situation.

Regardless of her personal feelings about testing, I hope that in time, Ms. Etheridge is able to recognize that many people (not all) feel that having genetic information about cancer risk can improve their health outcomes, and that she appreciates the value of a more balanced public position on BRCA testing.

 

FDA Approval of Promising Targeted Therapy Likely Stalled Until More Research Studies are Completed

Wednesday, June 25, 2014 was a pivotal day for our community.

It began with promise and ended with disappointment. For the first time ever, a treatment targeted for BRCA-associated cancers was considered for approval by the FDA. Yesterday the FDA’s Oncologic Drug Advisory Committee (ODAC) held a hearing to consider FDA approval of the drug olaparib for BRCA-positive ovarian cancer.

FORCE has been following the development of these drugs for the last decade.

Since then, we have followed the research, educated people about these agents, generated excitement about the research focus on HBOC, and facilitated clinical trial enrollment. For the HBOC community and the almost 1 million people in the US that FORCE represents, these targeted therapies offered hope. Still, completion of PARP inhibitor studies has taken a long time and in the duration, many people who could not access PARP inhibitors and did not meet criteria for any clinical trial have died of hereditary cancers.

FORCE testified at the hearing on behalf of the HBOC community.

Lisa Schlager VP of Policy at FORCE testifies.

Lisa Schlager VP of Policy at FORCE testifies.

FORCE was there to represent our community at this important hearing, as we have always been in the past. When the community needed protection against genetic discrimination, FORCE successfully lobbied for the passage of GINA laws. When laboratories began aggressive direct-to-consumer marketing of genetic testing, FORCE was there testifying to the Secretary of Health against these practices. We were at the steps of the US Supreme Court fighting for freedom from gene patents, and Wednesday we stood up in front of the ODAC hearing and urged the FDA to approve olaparib to treat hereditary ovarian cancer. You can read our full testimony here.


During the hearing, ODAC voted against olaparib approval in favor of waiting for further research results.

The FDA and ODAC recommended waiting until the completion of further studies before approving the drug, a process which could take several more years. The FDA will issue a final ruling on this application in October, however it is expected that they will not reverse their position on waiting until further studies are completed before approving this drug.

A point of contention is the issue of progression-free survival vs. overall survival.

The concept of progression-free survival (PFS) refers to the period of time that a treatment causes the cancer to improve or remain stable without getting worse. Overall survival (OS) measures the specific length of time that a person with cancer survives after receiving treatment. Scientist use these terms to measure the success or efficacy of new cancer therapies. Traditionally, the FDA has used only overall survival when considering the approval of a new drug. Other outcomes such as improved quality of life, and progression free survival are not usually considered significant enough for the FDA to approve a drug. There has debate among researchers and advocacy groups about whether or not a drug should be approved if it doesn’t demonstrate OS benefits. For patients facing advanced disease, PFS may seem like an acceptable endpoint.

In the olaparib study there was a statistically significant benefit in progression-free survival for BRCA mutation carriers who received olaparib: 6.9 months longer than those on placebo. The time until next treatment was 9.4 months longer in BRCA mutation carriers who took olaparib compared to those who received a placebo. Olaparib showed a significant effect on time to subsequent therapy in BRCA-mutation carriers, with the median time to subsequent therapy of 15.6 months in patients receiving olaparib versus 6.2 months in the placebo group.  There was a trend towards improved overall survival for women who took olaparib, with 55% of patients in the placebo arm dying compared to 50%, with a reported hazard ratio of 0.73 but this did not reach statistical significance in part because of the small number of patients in the study.

FORCE believes olaparib should receive FDA approval now. 

FORCE strongly supports the immediate approval of olaparib as a maintenance drug for BRCA-positive ovarian cancer because we believe it will improve the lives of women fighting ovarian cancer today. We will continue to do everything in our power to urge the FDA to consider the needs of our community.

In the meantime, we will continue to encourage our community to participate in and match patients to the critical research that we hope will lead to FDA approval of PARP inhibitors.

However, given the small subpopulations of women eligible for these trials, and the long timeline for completion of these studies, we are very concerned that completion of larger trials could take too long. Looking at the data on progression-free survival and time to subsequent first therapy, olaparib gives BRCA mutation carriers with ovarian cancer more time without disease and more time where they can avoid chemotherapy, translating to months or years with improved quality of life.

FORCE urged the FDA to consider the unmet needs of the HBOC community. In our testimony we asked the FDA,

“How many more women will die or suffer the effects of advanced disease and chemotherapy while we are waiting for larger trials to be completed? Women fighting hereditary ovarian cancer do not have time to wait.”

Research requires people! FORCE connects people to HBOC research.

With the FDA leaning towards delaying approval until the completion of further studies, now more than ever our efforts to enroll patients into HBOC studies is critical! Please help us create a better future for people affected by hereditary cancers by:

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Challenges to HBOC Research Enrollment: Competing Cancer Treatment Studies

Research is the key to better medical options. In prior blogs, I outlined some of the barriers to completing hereditary cancer research. This is the next blog in our series about addressing the barriers to hereditary cancer research.

Hereditary cancers make up a small subset of a larger disease state. About 7% of all breast cancer cases and about 18% of ovarian cancer cases are caused by a BRCA mutation. Research has shown that cancers caused by BRCA mutations may behave differently and respond to different treatments than cancers that are not caused by a mutation. So HBOC-specific treatment research is critical. After years of advocacy, new studies are looking at agents that may preferentially benefit people with BRCA mutations. Recruiting enough patients to complete these studies is a significant challenge. Open HBOC-specific clinical trials that desperately need participants must compete with more numerous, larger studies that are not limited to people with mutations.

Clinical trials are important for improving cancer treatment, and it’s important that all studies are completed. However, we need to balance the recruitment of BRCA mutation carriers into more general clinical trials so we don’t deplete the potential pool of participants for BRCA-specific studies. To maximize all clinical trial enrollment, it makes sense to better match patients to clinical trials that are specific and most relevant to their situation.

Breast Cancer Subtypes. The challenge of competing studies is apparent in breast cancer treatment research. Breast cancer is categorized into several different subtypes based on features of the tumor. Some clinical trials are open to one or more subtypes of breast cancer.  The main subtypes include:

  • Breast cancers known as “Her2neu positive” make too much of a protein called Her2/neu which promotes cancer cell growth.  These cancers respond to drugs like Herceptin, designed to target the Her2/neu protein. Most BRCA mutation carriers do not develop Her2neu positive breast cancer, so clinical trials focused on Her2neu are less likely to draw from the BRCA positive population.
  • The most common type of breast cancer are “ER/PR positive.” These cancers have receptors that bind the hormones estrogen and progesterone. These cancers tend to respond to hormonal treatments such as tamoxifen and aromatase inhibitors. About 80% of breast cancer patients with BRCA2 mutations will have ER/PR positive tumors.
  • “Triple Negative Breast Cancers” (TNBC) do not express estrogen or progesterone receptors and do not overexpress a protein called “Her2neu.” TNBC are usually treated with chemotherapy, and not with hormonal medications or drugs like Herceptin that target the HER2 protein. TNBC are common in women with BRCA1 mutations. About 85% of breast cancer patients with BRCA1 mutations will have TNBC.

Although people with BRCA mutations can develop breast cancer in any of these subtypes, people with mutations tend to develop specific subtypes of breast cancer. As most cancer is not hereditary, mutation carriers make up a minority of the patients in each of these subtypes.

Breast cancer clinical trials.  A simplified way to illustrate the issue is to view clinical trials like puzzles that need to be completed…

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As potential participants, we make up the puzzle pieces. 

puzzle_pieces

A majority of breast cancer clinical trials are open to people with any type of breast cancer, but others enroll only people with specific subtypes. Clinicaltrials.gov, a searchable database run by the National Institutes of Health, lists all clinical trials enrolling patients. A recent search of this database identified 262 U.S. treatment clinical trials for any type of advanced breast cancer.

262 studies


These trials are open to all breast cancer subtypes, so most women with any type of advanced breast cancer – including mutation carriers – would be eligible.

allsubtypes

ER/PR-positive clinical trials. A search on clinicaltrials.gov showed 38 U.S. studies for advanced breast cancer treatment that are open to women with ER/PR-positive breast cancer.

38ERpositive

Although these studies will draw from the pool of ER/PR-positive patients, mutation carriers are also eligible to participate, since many BRCA2 and some BRCA1 mutation carriers also have ER/PR-positive tumors.

erprpuzzle

Triple negative clinical trials. A search of clinicaltrials.gov showed 31 U.S. studies for treatment of advanced breast cancer specifically for women with triple negative breast cancer.

31tnbc

These TNBC studies draw participants with and without BRCA mutations. Because many BRCA1 and some BRCA2 mutation carriers have TNBC tumors, their participation in these open studies decreases the potential pool of participants for BRCA-specific studies.

tnbcpuzzle

BRCA clinical trials. A search of clinicaltrials.gov shows just 9 U.S. studies for advanced breast cancer treatment that are specific to women with BRCA mutations.

9brca studies

brcapuzzle

If these studies cannot complete enrollment due to lack of participants, they are at risk of being closed.

Ovarian cancer. The recruitment/participation situation applies to other clinical trials including ovarian cancer treatment trials. About 18% of ovarian cancers are caused by a BRCA mutation.

ovarianpuzzle

In a recent search on clinicaltrials.gov, of 60 advanced ovarian cancer treatment studies in the United States listed on clinicaltrials.gov, 8 specifically targeted patients with BRCA mutations.

More general advanced ovarian cancer clinical trials will draw from women with and without BRCA mutations.

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This leaves fewer BRCA mutation carrier participants available to complete the studies specifically designed for mutation carriers.

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The prospect of not being able to complete HBOC-specific clinical trials is troubling for the HBOC community, and could be disastrous to the research we need: a mutation carrier with breast or ovarian cancer has a higher likelihood of finding and enrolling in a less-specific clinical trial than one of the few studies open to someone with their specific cancer and mutation type.

In order for progress to be made, and for new drugs to be tested and successful drugs to be approved, all of these clinical trials must be completed. Everyone benefits if we can get the maximum number of studies enrolled without sacrificing participation in smaller, less numerous, or very specific clinical trials for very specific subtypes of cancer. The solution to this challenge requires a concerted effort to match clinical trial cancer patients to the studies that are best suited for them. Because HBOC-specific clinical trials are less numerous, FORCE is developing a comprehensive searchable database of research studies specifically designed to treat, detect, or prevent HBOC cancers. We will be training volunteers to help match members of our community to the clinical trials that are specific to their situation.  We are working to educate the HBOC community about these specific studies, and encourage health care providers who treat members of our community to notify patients about HBOC-specific research at the time of diagnosis, even if the clinical trial is being conducted at a separate or competing facility.

In this way we can continue to move the barometer of research and complete these HBOC-specific studies with a goal of FDA-approved treatments that improve survival and/or quality of life. And having more agents with FDA approval translates to more tools for oncologists to help members of our community prevent and survive hereditary cancer.