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.

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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.

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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.

 

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. 

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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.

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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.

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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.

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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.

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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.

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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.

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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

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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.

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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.

 


FORCE 15: Reasons to Join FORCEs and Attend Our 8th Annual Conference

Need a reason to attend this year’s Joining FORCEs Conference? Here are 15 good ones:

  1. It’s the largest annual gathering by and for the hereditary cancer community.  Be a part of this landmark event.
  2. We make the latest science understandable and accessible. Hear experts clearly explain the science of hereditary cancer and make the latest research and medical options understandable and accessible no matter where you are in the HBOC journey.conference1
  3. We cover every aspect of HBOC. View our agenda to see a complete list of the 48 separate lectures, workshops and networking sessions.
  4. Sessions are organized to help you find the information you most need.  Our conference content is aligned into tracks that focus on different groups.  View a list of suggested sessions based on your specific situation.
  5. We bring researchers to you.  You’ll hear the latest scientific findings presented first-hand by world-class experts, and have the unprecedented opportunity to speak one-on-one with researchers about your own pressing issues.dr_levine_round_table_small
  6. Benefit from the experience of others.  Meet, chat and bond with hundreds of others who share your concerns.  Hear the poignant personal stories of people just like you who have faced hereditary cancer.  Talk face-to-face with your virtual friends who have supported you on Facebook or the FORCE message boards. Build relationships that will last a lifetime.
  7. See and hear about women’s real post-mastectomy surgical results.  If you’re considering your surgical options, visit our Show & Tell room to chat with women who have already undergone mastectomy. Every type of reconstruction and mastectomy without reconstruction is showcased.  Meet and speak with plastic surgeons who perform these surgeries, and Kathy Steligo, author of The Breast Reconstruction Guidebook. Participate in our photo shoot to help other women make decisions about surgery.
  8. Gain information and support to help make important health care decisions.  Learn the latest information, guidelines, and emerging science to help you overcome one of the biggest challenges of living with HBOC: sorting through medical options so that you can make health care decisions that are right for you. From risk-management to fertility options, from emerging tools for cancer detection to long-term survivorship issues, from hormone replacement to enrolling in a clinical trial, our conference sessions will help you make decisions with the most up-to-date information.
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  9. Enroll in research.  Make a difference.  Learn about and enroll in studies that will offer better answers for ourselves and future generations.
  10. Give back to the community by volunteering. Learn about FORCE volunteer opportunities and meet our volunteer team.
  11. Meet our Spirit of Empowerment Award winners. Every year we honor people who contribute to the HBOC community and support the work of FORCE. This year we honor annual_awards_compassionawardcancer survivor Annie Parker, whose personal struggle with hereditary cancer is the basis for the Hollywood film, Decoding Annie Parker; Kara DioGuardi, GRAMMY-nominated songwriter, previvor and former American Idol judge; Stacey Sager, Channel 7 Eyewitness News reporter and two-time cancer survivor; the sister team of Sisco Berluti Jewelry, and others.
  12. Bond with family members. Sharing the conference with family members is a unique bonding experience that will help your loved ones to better understand your choices, and empower them to make their own informed health care decisions.

  13. Enjoy the new venue
    . Located in the heart of Philadelphia, our conference site  offers many amenities and is within walking distance to downtown dining, shop
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    ping and attractions, including Independence Hall and the Liberty Bell.  The clbcbellhonference offers great food, relaxation, opportunities to decompress, express yourself and play.
  14. Get fit, reclaim your health and well-being. Learn how you can make choices for a happier, healthier life. Sessions about exercise, nutrition, and integrative medicine provide information on living a healthy lifestyle. Improve your flexibility with yoga or try a heart-pumping Zumba workout. Attend the sexuality session or one of our “GirlsNight In” parties and reclaim your mojo.
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  15. Celebrate FORCE’s 15th Anniversary.  Help us blow out the candles and share birthday cake as we celebrate 15 years of fighting on behalf of the HBOC community.

A limited number of scholarships are available for those who would most benefit from attending but require financial support in order to participate. Visit our scholarship page to donate or apply.

See you in Philadelphia!

Preventive Guidelines Discriminate Against Cancer Survivors

FORCE has created a change.org petition to ask the United States Preventive Services Task Force to change their guidelines to include cancer survivors. You can read more about the issue and the petition below.

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The United States Preventive Services Task Force (US

The panel wields considerable power over consumer access to preventive health care services—primary care clinicians and health systems follow its guidelines. And importantly, the guidelines are incorporated into 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.”PSTF) is a government-supported independent panel of experts that reviews and develops recommendations on select preventive health services. In the panel’s own words: “The USPSTF is committed to improving the health of all Americans. To achieve this, the USPSTF assesses evidence on specific populations and makes specific evidence-based recommendations for specific populations.

The USPSTF has reviewed several, but not all preventive services available to keep us healthy, so some gaps are unavoidable. (Read a list of USPSTF-reviewed services here.)

The panel does have guidelines for risk assessment and BRCA testing, which are now being updated. Revisions have been improved based on feedback and suggestions from many groups and health care professionals; the proposed update supports genetic counseling and testing with a “Grade B” in women who have a family history consistent with a mutation, requiring insurance companies to cover these preventive services without a co-pay or deductible. But as we have previously reported, serious gaps remain, including omission of:

  • men
  • risk assessment and Lynch Syndrome testing
  • letter grade assignment for screening and prevention for high-risk women

We will continue to post about these gaps in policy that affect our community’s access to care. This blog post highlights one particular aspect of the USPSTF draft guidelines on risk assessment and BRCA testing: the discrimination against cancer survivors.

Regarding its draft guidelines, the USPSTF states: “These recommendations apply to women who have not received a diagnosis of breast or ovarian cancer but who have family members with breast or ovarian cancer whose BRCA status is unknown. Women presenting to their primary care providers who have a relative with a known potentially harmful mutation in the BRCA1 or BRCA2 genes should receive genetic counseling and consideration for testing.

FORCE response to the USPSTF draft guidelines

In October of this year FORCE sent a letter to the USPSTF which included four key points about this gap:

  • We pointed out that cancer survivors with a BRCA mutation are at high risk for an unrelated second primary cancer, and could benefit from preventive aspects of BRCA testing.
  • We requested that the task force review the strong research evidence supporting genetic risk assessment for preventive purposes in women who have been already been diagnosed with breast cancer and meet national guidelines.
  • We emphasized how omission of survivors from these guidelines will negatively impact their access to care and coverage for preventive services under the PPACA.
  • We requested that women with a cancer diagnosis be included in the definition of “population under consideration.”

USPSTF response to FORCE

The USPSTF responded to our letter with this statement, “Although the Task Force recognizes the importance of the further evaluation women who have the diagnosis of breast or ovarian cancer, that assessment is part of disease management and is beyond the scope of this recommendation. The Task Force recognizes that genetic counseling and testing may be an important part of disease management for women who have been diagnosed. However, the Task Force’s mission is to determine the evidence-base for preventive services in the general population who have no signs or symptoms of disease.

I recognize that the USPSTF is focused on prevention only, and that any service that may come under the category of treatment is beyond their scope. And it is true that under some circumstances—particularly in women newly diagnosed with breast cancer—BRCA testing can affect treatment decisions, including the decision to have lumpectomy or unilateral mastectomy vs. bilateral mastectomy. However, the USPSTF response is missing a critical point: BRCA testing has preventive value beyond “disease management” and can help survivors prevent a new, completely unrelated second diagnosis of breast cancer. Experts still recommend genetic risk assessment for women whose personal and/or family medical history indicates a possible mutation even after they have completed their treatment for cancer and have no evidence of disease. These women meet the task force’s criteria of having no signs or symptoms of disease.

The USPSTF guidelines discriminate against cancer survivors

The USPSTF’s insistence to exclude survivors from these guidelines, despite research evidence to show the preventive value in testing people after cancer, amounts to discrimination against cancer survivors. The panel implies that once a person is diagnosed with cancer, all further health efforts fall under the category of treatment of the disease. By dismissing the preventive value of BRCA testing in this population they also dismiss the value of preventive services in cancer survivors in general, many of whom will go on to live long healthy lives if they are given access to appropriate preventive services.

My personal history is a perfect illustration. When I was first diagnosed with breast cancer, my health care providers failed to recognize that I had several red flags for a mutation. It wasn’t until after my unilateral mastectomy—when I read an article about BRCA testing—that I recognized I fit the guidelines for BRCA testing. I learned after my treatment that I had a BRCA 2 mutation; I was fortunate because a prophylactic mastectomy of my so-called healthy breast found early-stage cancer. During my BSO, abnormal cells were found in my abdominal wash, indicating that dangerous changes that could develop into cancer if left unaddressed were already underway. These surgeries were preventive in every sense of the word. The fact that I had already been diagnosed with breast cancer did not take away from the preventive benefit of BRCA testing for me. Now 15 years out from my preventive surgeries, I remain healthy and cancer-free. I am confident that the preventive steps I took have kept me from developing a second primary cancer.

Thousands of women like me who have completed treatment for cancer meet expert guidelines for risk assessment and BRCA testing, and also fit the USPSTF’s criteria of having “no signs or symptoms of disease.” Research evidence shows that genetic risk assessment and preventive action can lower their risk for a new primary cancer, detect it early, and lower their mortality. In many cases these women are the key to identifying a family mutation. As U.S. citizens, they are entitled to similar preventive services as people in the general population. Continued exclusion of this population discriminates against breast and ovarian cancer survivors and jeopardizes not just them, but also their healthy relatives.

The guidelines run counter to the spirit of the PPACA

As of January 2014—due to provisions in the PPACA – U.S. citizens with a pre-existing condition can no longer be denied or dropped from their health insurance plans. The stated goals of the PPACA are: “The most prevalent goal, however, and the one concept that is nearly universally accepted is the desire to improve the quality of care across the United States (U.S.) for all citizens until it meets the highest of standards.” It is ironic that at a time when the Patient Protection and Affordable Care Act is being implemented to eliminate pre-existing condition exclusions by insurance companies, the USPSTF task force is in effect adding back pre-existing status, and therefore barriers to cancer survivors’ access to preventive care.

What you can do

After several letters to the USPSTF, we have decided to appeal to the task force once more, focusing on the issues with the most supportive research evidence. We ask that you read and sign on to our counter-response letter, which we plan to submit by December 12. (Read more about the issues here). We ask you to share this letter with any cancer survivors, previvors, health care providers, caregivers, and everyone you know and ask them to sign on to the letter as well. This issue and the USPSTF actions to assure access to preventive services for all citizens effects us all. We will request a written response from the USPSTF and will share it with our community. We will continue to post about the gaps in policy that affect our community’s access to care.

To sign on to the letter, send an email to suefriedman@facingourrisk.org and include your full name, city, and state.

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.