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.

 

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.

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.

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.

 

 

Health Care Providers Can Help Accelerate Hereditary Cancer Research

1 in 500 people (0.2% of the population) carries a BRCA mutation, yet we constitute about 10% of people with breast or ovarian cancer. The HBOC community shoulders a disproportionate cancer burden.

Why HBOC research is important
Hereditary cancers constitute a small subset of a larger disease state. About 7% of breast cancers and 18% of ovarian cancers are due to a BRCA mutation. The HBOC community shoulders a disproportionate cancer burden, facing lifetime cancer risks that are higher than any other known population. Our cancers tend to be younger onset and more aggressive, we are at risk for second and third primary cancer diagnoses, and our risk can be passed on to our children and shared with relatives. We are a subset of the larger cancer community, yet our cancers develop differently, more quickly, and may respond differently to treatments than sporadic cancers.

After years of advocacy, HBOC research is getting some well-deserved attention. But to continue this progress, we need to ensure that these studies enroll adequate numbers of patients. A previous blog touched on the complex, multifaceted challenges to HBOC research recruitment and the shared responsibility of all stakeholders to overcome these barriers. This blog focuses on specific barriers to HBOC research and the integral role health care professionals can play in overcoming these barriers to accelerate progress in preventing and treating hereditary cancers. 

Health care providers as partners in research recruitment
Patients trust and rely on their medical teams to provide the best care specific to their individual situations. Research shows that physicians play a key role in educating patients about research studies. Yet, the same studies also show that physicians do not always inform patients about clinical trials elsewhere due to institutional barriers and personal biases. For this reason we are asking health care providers to join FORCE in our campaign to promote awareness and participation in research among the HBOC community.  We ask that oncology health care providers consider the following for all their patients:

• Refer patients who meet NCCN criteria for genetic evaluation as soon as possible after diagnosis.
• Discuss the availability of clinical trials with newly diagnosed or newly relapsed patients.
• Consider which clinical trial, including those outside the health care provider’s facility or practice, that might be the best match for a patient,
• Inform patients if a particular treatment might impact their eligibility for a clinical trial. 
• Refer patients to FORCE as a resource and to assist with clinical trial matching.

HBOC specific research studies
HBOC cancers develop due to the presence of a germ-line mutation in one of the BRCA genes. Scientists are researching how to exploit these deficits to better prevent or treat hereditary cancers. For example, PARP inhibitors, first studied in 2005, attack the weaknesses of BRCA-related cancer cells in repairing DNA damage. Despite promising results, delays and roadblocks have delayed the path to FDA approval; more than eight years later, we still have no FDA-approved PARP inhibitors, and people are still dying of hereditary cancers. Research of PARP inhibitors is finally progressing, with more HBOC-specific open studies urgently pursuing patient enrollment.  Failure to completely accrue these studies could derail future HBOC research by creating the perception that the HBOC community is not motivated to participate in research, and that as a cohort, we are too difficult to recruit. Health care providers can play a powerful role in surmounting enrollment obstacles by simply informing their patients about clinical trials.

Challenge: Competing clinical trials and matching patients
HBOC-specific clinical trials compete with each other for participants, and compete with larger, more numerous studies that are not limited to people with mutations. For example, a recent search of clinicaltrials.gov for U.S. treatment trials enrolling people with metastatic, BRCA-associated breast cancer returned 11 studies. A similar search for all metastatic breast cancer studies returned over 200 clinical trials with broader recruitment criteria. Of 60 advanced ovarian cancer treatment studies listed, just eight were specifically for patients with BRCA mutations. The implications are concerning for the HBOC community: a mutation carrier with advanced 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. 

Solution: Maintain awareness of HBOC clinical trials and refer appropriate patients to studies, even those at other institutions
We encourage all health care providers who work in oncology to stay updated on clinical trials that are recruiting HBOC patients. FORCE provides two helpful tools to do so: our Health Care Provider electronic updates (sign up here and choose the “Updates for Health Care Providers” option), and our online list of HBOC research.  Next month we will be launching an HBOC-specific clinical trials searchable database to better match patients to relevant clinical trials.

If your institution or practice has HBOC-related research that you would like to have included in our database, please send an overview and contact information for the study to Lisa Rezende at lisar@facingourrisk.org.

Challenge: Clinical trials are seen as a “last resort” and certain treatments may impact eligibility for studies
An erroneous perception exists that clinical trials are a “last resort” for treating patients who have progressed after several different therapies. Many patients report that they have been discouraged from participating in a trial because they haven’t exhausted all their treatment options yet. Additionally, in addition to studies for  those with advanced cancer, there are clinical trials enrolling HBOC patients for cancer prevention, earlier-stage disease, and maintenance therapy for patients who have completed treatment.

Further, certain treatments may affect a patient’s eligibility for some clinical trials. For example, newly-diagnosed breast cancer patients who undergo lumpectomy or mastectomy become ineligible for neo-adjuvant chemotherapy studies. Receiving a certain chemotherapy or a certain number of prior treatments may render patients ineligible for some PARP inhibitor studies.

Solution: Discuss clinical trials before beginning treatment
Because patients who do not receive the most up-to-date and comprehensive information about clinical trial options are less likely to make informed decisions about their care, health care providers should consider notifying patients about clinical trial options before starting treatment or resuming treatment after a recurrence. We encourage health care providers to inform hereditary cancer patients sooner rather than later about the existence of HBOC-specific research, even those at separate or competing facilities. Health care providers and patients can find relevant research studies listed on the FORCE website.

Challenge: Underutilized genetic testing
Research has shown that genetic counseling and testing are underutilized services for those who meet national guidelines. Every woman diagnosed with breast cancer at age 50 or younger, and every woman diagnosed with ovarian cancer at any age meets national consensus guidelines for referral for genetic counseling. Despite these national guidelines, a recent study showed that 57% of women diagnosed with breast cancer at age 50 or younger did not receive genetics evaluation.

Solution: Refer all patients who meet national guidelines for genetic counseling and testing

Every breast cancer patient who has a family history or who was diagnosed at or before age 50, and every ovarian cancer patient meets NCCN guidelines for referral for genetic evaluation. Although BRCA test results may affect some breast cancer surgical decisions, impact risk for future cancers, and can inform a patient’s relatives of their risk for cancer, genetic counseling and testing of newly diagnosed breast and ovarian cancer patients often does not receive high priority. Treatment clinical trials that specifically recruit people with BRCA-associated cancers provide one more reason for health care providers to recommend genetic evaluation to newly diagnosed breast and ovarian cancer patients.

Solving the problem of hereditary cancer requires a maintained, concerted effort. We hope our health care provider partners will read, consider, and share this blog with colleagues and follow these steps to accelerating research.

Patient-Centered Outcomes Research Institute (PCORI): Research Done Differently

What is PCORI?

The Patient-Centered Outcomes Research Institute (PCORI) is a new government-supported agency that approaches medical research with a focus on the patient to improve health outcomes. Aiming to answer medical questions that are most important to patients and collecting data from “real world settings,” this differs from traditional research, which typically occurs at large academic medical centers where scientists determine the research questions and priorities to be studied.

PCORI 101 is an easy-to-follow short video that outlines the institute’s research approach and goals.

Why was PCORI formed?

Hundreds of millions of dollars are poured into traditional research each year in the United States—research that is important to advance our knowledge of health and disease—but isn’t always focused on providing patients with the specific information they need to make medical decisions. PCORI was formed to change that. Like all research, PCORI-funded projects must be scientifically rigorous and conducted ethically. But PCORI’s patient-centered approach to resolving medical questions is unique, involving consumer input at every step:

• formulating research questions
• setting priorities
• planning studies
• collecting information
• interpreting results
• sharing findings

PCORI research focuses on answering four common patient questions:

• Given my personal characteristics, conditions, and preferences, what should I expect will happen to me?
• What are my options, and related potential benefits and harms?
• What can I do to improve outcomes that are most important to me?
• How can my health care providers help me make the best decisions about my health and healthcare?

How Can PCORI Research Help the HBOC Community?

Patient-Centered Outcomes Research (PCOR) is very important for the Hereditary Breast and Ovarian Cancer (HBOC) community. Individuals with BRCA mutations or other risk factors must make many important and difficult medical decisions. In the last two decades research has discovered important information about hereditary cancer risk and outcomes, but our message boards and forums are still filled with lingering questions for which we have no definitive answers, including:

• What is the ideal age to remove my ovaries/tubes?
• Is removing my uterus along with my ovaries and tubes beneficial, and if so, how?
• What medical outcomes might I face after undergoing surgical menopause?
• Will my health and quality of life be improved or harmed by taking hormone replacement after surgical menopause?
• Is increased surveillance likely to find a cancer early enough to avoid chemotherapy?
• Are certain treatments better for people with hereditary cancers? Is it in my best interest to avoid certain treatments?

Answers to questions like these can help people facing HBOC make informed decisions about their health care based on their personal health goals and priorities.

Government agencies such as the United States Preventive Services Task Force (USPSTF) have a strong influence on insurance coverage and patient access to preventive services. The USPSTF reviews traditional research evidence to set screening and prevention guidelines. It also considers Patient-Centered Outcomes Research information that includes people’s attitudes towards preventive medicine such as:

• Does an increased chance of abnormal findings affect a person’s willingness to undergo more sensitive cancer screening tests such as MRI? Does the risk of increased biopsies outweigh the benefit of detecting cancer earlier and if so, for which patients?
• Which prevention outcomes are most important to patients?
  • survival
  • avoiding chemotherapy or other debilitating treatment
  • quality of life
• Are answers to these questions different for high-risk patients than average-risk patients?

Research on the HBOC community’s perspectives on medical services can guide agencies in setting policies that affect access to care.

How is FORCE Involved in Patient-Centered Outcomes Research?

Over the past 15 years, FORCE has organized and united the HBOC community to identify, highlight, and promote research on the health concerns and outcomes that matter to people affected by HBOC. As we have compiled the research that is known about these issues, we have also identified the limits of our knowledge. Through our forums, programs, and surveys we have collected public input on the concerns and information gaps that most impact access to care and medical decision-making. Through our collaborations and participation on task forces and guidelines panels we continue to advance research and promote policies that benefit our community.

Recently FORCE’s collaboration with researchers from the University of South Florida and the Michigan Department of Community Health received a funding award from PCORI that will enable a “patient-powered research network” called the American BRCA Outcomes and Utilization of Testing (ABOUT) Network. Our collaboration is one of 29 networks that were recently approved to participate in a new national resource through PCORI known as the National Patient-Centered Clinical Research Network (PCORnet). We were chosen primarily due to our commitment to gathering patient input and identifying important concerns, our work to unite the community, our dedication to sharing important research results back to the community, and our efforts to train and prepare community members who have no scientific background to provide input into research.

Over the next 18 months we will be engaging our members in the following ways:

• recruiting members who are interested in completing advocacy training and participating in leadership roles to help us build the governance of the ABOUT Network.
• soliciting community input to identify and prioritize important unanswered research questions
• offering opportunities for people to enroll in the ABOUT Network to help accelerate Patient-Centered Outcomes Research
• training people with no scientific background to participate in research advocacy through our FORCE Research Advocacy Training (FRAT) program. FRAT helps to prepare members of our community to become involved in all levels of research planning and implementation.

FORCE’s participation in the ABOUT Network will allow HBOC stakeholders a place at the table and an unprecedented voice in guiding PCOR research over the coming years. Stay tuned for more details soon.

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.

 

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.

Meeting the Challenges to Hereditary Cancer Research

This week is National HBOC week and today is National Previvor Day; personally this season is marked by equal doses of reflection, recollection, gratitude, and action.

Much progress has been made in cancer research in the 15 years since I learned about my mutation and founded FORCE. Perhaps most exciting are the advances in “personalized medicine,” which looks at unique genetics traits of a subset of the general population to develop more tailored medical care. Personalized medicine research has given us new tools in the cancer fight, for example tumor tests like OncotypeDX, which looks at the unique biology of tumors to help predict which ones are most likely to recur and which patients would benefit most or least from additional treatment. New “targeted therapies” work by interacting with receptors and molecules found in certain cancer cells. They interfere with cell function causing the cancer cell to die. An example is Perjeta, which was just approved by the FDA to treat breast cancers that overexpress a marker called Her2neu.

Personalized medicine research has great potential for improving treatment, prevention and detection of hereditary cancers. HBOC cancers develop differently and behave differently than other cancers: they are younger-onset and more aggressive, there is a very high lifetime risk for one or more cancer diagnoses. And HBOC risk can be passed on to our children. Researchers are looking at the genes that make our cancers different to provide better ways to treat or prevent them. After years of advocacy, HBOC research is getting well-deserved attention. The observation by researchers that many hereditary ovarian cancers may actually develop in the fallopian tubes has led to the opening of a study looking at whether fallopian tube removal may be a safe and effective strategy for lowering risk in women with BRCA mutations who are not ready to remove their ovaries. Another notable example, PARP inhibitors are targeted drugs designed to treat cancers caused by BRCA mutations.

FORCE featured research highlights studies of particular interest to the HBOC community.

Clinical trials such as the BROCADE Study and ARIEL Studies and others are looking at whether PARP inhibitors may work better than standard care for breast, ovarian and other cancers. We need these studies to be completed before these agents can be made widely available, but researchers report that study participants are still desperately needed.

Over the years our research surveys have shown that our community:

• wants better, less invasive, more effective options for detecting, preventing and treating hereditary cancers.
• understands that these options require clinical trial research in order to advance.
• is very motivated and willing to participate in the studies that can benefit us now and in the future.

So what is delaying progress? I recently gave a presentation about the challenges of recruiting the HBOC community for clinical trials, which gave me the opportunity to explore and define some of the barriers to filling these studies.

• There is still a limited awareness about HBOC. Many people who meet expert guidelines are not being referred for genetics evaluation and testing.
• Many more cancer clinical trials are open to people regardless of mutation status than clinical trials specifically for people with mutations. For that reason, HBOC studies compete for patients with larger, more numerous, less specific research studies.
• Health care providers are often unaware of HBOC-specific research studies at different institutions or hospitals, or are hesitant to refer patients to them.
• Some clinical trials require patients to meet certain conditions, including limiting the type or number of prior treatments a patient can receive before enrolling. Patients who are not aware of clinical trial options before starting treatment or resuming treatment after a recurrence may be ineligible for study participation.
• Many individuals’ interest in clinical trial participation is limited by their concerns about safety, medical care, use of placebos, cost, and their ability to withdraw from a study.
• Finding open research studies, figuring out eligibility, and determining how to enroll can be challenging and time-consuming. Even websites that are created to simplify the process can be difficult to navigate.
• Some studies require travel to another hospital, city, or state to participate, and require patients to consult with a new team of doctors, creating additional costs and time away from work and home.

Despite the challenges, these studies are essential and the investment in HBOC research is clearly worthwhile. The good news is that identifying these challenges can help us begin to address them and move the needle in favor of study enrollment and completion. FORCE is focusing efforts on overcoming these barriers. Below are some of the ways we are already tackling these issues. 

• Raising public awareness about national expert guidelines on cancer risk assessment and genetic testing
• Uniting and educating stakeholders to advocate for more resources and research specific to HBOC
• Educating the community about the importance of participating in HBOC-specific research
• Empowering patients to proactively seek out or ask their oncologist about clinical trials
• Providing training to consumers affected by HBOC to participate in panels, research peer review and advisory boards to represent community perspective in setting research priorities and developing and conducting research studies
• Informing people about new and promising targeted agents and HBOC-specific research opportunities
• Working with researchers and industry partners to develop and distribute patient-friendly websites and materials that can be shared with the HBOC community
• Educating health care providers about the challenges facing the HBOC community; our urgent need for new and better treatment, detection, and prevention options; and how they can help us with our efforts to improve HBOC research enrollment
• Educating health care providers about open clinical trials enrolling people with HBOC
• Educating policymakers and regulatory agencies about the challenges facing the HBOC community, and our need for expedited drug development, research, and approval

Over the next few months, I will be blogging in more depth about each of these barriers and strategies for addressing them. FORCE will be working to better assess the issues and create new programs so that we can make a positive impact on HBOC research participation. To learn more about how you can help advance HBOC research, visit the FORCE website for updates. To find research on cancer prevention, detection, treatment, quality-of-life and other studies visit the featured studies section and other studies section of our website or visit the clinicaltrials.gov website.

Maximizing Access to BRCA Testing by Involving Genetics Experts

Note: The below is an updated version of a post in 2008 right after the documentary In the Family was released, and actress Christina Applegate announced she had a BRCA 1 mutation. Five years later, this post is more relevant than ever. 

As the dust clears since Angelina Jolie went public with her BRCA status, the impact of her revelation has been mixed. On the positive side, the increased awareness of HBOC has opened up a public dialogue on genetic counseling, testing, cancer prevention, and access to care and has encouraged people to educate themselves about these topics. More people are considering their family history of cancer, pursuing genetic counseling and testing, and learning their options to prevent or to detect cancer earlier. Following these steps will save lives. Unfortunately, people’s initial inquiries about testing are not always met with credible information. We know from experience that where people go for additional information, resources, and support matters for their outcomes. FORCE has documented cases where people received inaccurate information about genetic testing which led to negative health consequences.

Fortunately, many people are finding their way to the expert-reviewed information and resources from FORCE and are being referred to genetics professionals. Calls to our toll free helpline have increased in direct proportion to media reports about BRCA. One of the frequent requests we receive is about financial assistance for genetic testing. Many of these calls are from individuals who have a family history of cancer and health insurance, but their insurance has denied covering genetic testing.

Many of these insurance denials and high out-of-pocket costs related to testing occur because people have not first met with a qualified expert in cancer genetics. When you consider the $3,000+ cost for “full-sequencing” BRCA 1 and BRCA 2 testing, where the entire gene is evaluated, it’s easy to understand why genetic testing is beyond the means of many people. However, under certain circumstances, a less extensive test may be more appropriate and can lower the price of testing by thousands of dollars. In other cases the choice of which member of the family receives genetic testing first can also affect cost and insurance coverage and risk assessment for the entire family. Some of these insurance denials stem from an uninformed health care provider ordering the wrong test or not identifying the best first person in a family to receive testing.

The high cost of genetic testing for BRCA is due to the fact that only one company—Myriad Genetics—can perform the gene test in the United States. They were granted exclusive patents on the BRCA genes and consequently control everything about BRCA testing, including the price. Even as the cost of genetic technology has decreased, Myriad keeps raising the price of their BRCA test.

A specially trained genetics expert will first assess an individual’s family medical history, determine which test is most appropriate, and identify which family member should be tested first. Seeing a genetic counselor prior to genetic testing can make the difference between having a test denied or covered by insurance. In fact, for people who meet specific National Comprehensive Cancer Network (NCCN) standard-of-care guidelines, many insurance companies, will pay for both genetic counseling and testing. The Patient Protection and Affordable Care Act also outlines that people who meet certain guidelines qualify for genetic counseling and testing which must be covered by their insurance without copay or deductible. A team of genetics and cancer experts can be good advocates for insurance coverage of genetic testing.

When genetic testing proceeds without counseling there is a higher likelihood of inappropriate or costlier testing. Myriad is the only entity who stands to benefits from inappropriate BRCA testing. In 2009, FORCE presented testimony to the Secretary of Health’s Advisory Committee on Genetics outlining our concerns about the aggressive marketing that was leading to increased cost and harm to our community. These concerns still remain true.

The American Civil Liberties Union (ACLU) has filed a lawsuit to invalidate Myriad’s patents. FORCE has filed an Amicus Brief in support of the ACLU’s case. The Supreme Court has heard the case and they are expected to rule by this summer. Until the cost of genetic testing goes down, genetic testing will remain out of reach for too many people, even for those who meet standard-of-care guidelines. On a national level, financial support is limited. People who meet certain criteria and have annual income below the poverty level may qualify for testing under Myriad Genetics Laboratories financial assistance program. For people whose insurance does not cover the full cost of testing, co-pay assistance is available through the Cancer Resource Foundation. Regionally, FORCE has been able to navigate many people who contact us for assistance to programs in their area but there are still many gaps in access to care.

For the uninsured or underinsured women who receive assistance for genetic counseling and testing, what then? Experts recommend annual mammograms and MRI for BRCA-positive women ideally beginning at age 25. Patient Services Incorporated (PSI) has a program funded by Right Action for Women which covers the cost for MRI for eligible young high-risk women. The National Breast and Cervical Cancer Early Detection Program, provides free mammograms for women over 40. Gaps still remain for financial assistance for breast MRI for high-risk women over age 40 and for mammograms for women younger than age 40. Financial resources for women who choose to undergo  prophylactic surgery is even more limited. Like most disparity issues in health care, the needs are many and existing resources are few.

With the media spotlight on hereditary cancer, and demand for BRCA testing increasing, FORCE has continued to emphasize the importance of referral to appropriate experts for genetic counseling before and after genetic testing. Until the disparity and cost of testing issues are resolved, given that genetic testing is expensive, financial resources are limited, and not everyone has equal access to care, the best way to maximize the number of appropriate tests, is to include genetic counseling with experts prior to the ordering of genetic tests.

Proposed Guidelines on BRCA Testing Leave Many Gaps

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

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

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

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

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

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

FORCE Concerns with the Draft Guidelines

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

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

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

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

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

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

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

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

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

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

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

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

Hopeful Progress in Ovarian Cancer Prevention Research

In 2008 FORCE conducted a survey to learn about research priorities for the HBOC community. We learned that women want better methods for ovarian cancer detection and prevention for ourselves, our children, and future generations. For this reason, we have worked closely with researchers exploring new options and we have carefully followed and shared with our community the progress in ovarian cancer detection and prevention.

Since BRCA testing became available, experts have recommended bilateral salpingo-oophorectomy or BSO (removal of the ovaries and fallopian tubes) for women with mutations between the ages of 35 – 40 or after childbearing is completed. Until large studies on women with mutations were completed, there was little data and only common sense to back up this recommendation. Later, research proved that for women with BRCA mutations removing the ovaries and tubes lowers the risk of developing and dying from breast cancer and ovarian cancer. I recall when the studies were published and the media was flooded with articles about how this “simple surgery” can lower risk. At the time, I was about 3 years out from my BSO at age 35 and dealing with significant surgical menopause side effects. I recall thinking, “Simple for whom?”

Don’t get me wrong; BSO is often an outpatient procedure with minimal surgical risk and scarring. The research on risk and survival is incredibly important and significant, and finally proved what experts long suspected. But the use of the term “simple” made it seem like these decisions were easy. On a personal and professional basis, and almost daily, I am reminded how difficult the decisions are. Many women recover quickly after surgery and their quality-of-life remains the same. But others suffer from side effects and long-term health and quality-of-life consequences from early menopause. The decision for surgery can be difficult and consequential for many women.

In the last few years, studies on high-risk women suggest that many ovarian cancers in BRCA gene mutation carriers may actually start in the fallopian tubes. In 2009 and 2010 at our annual conference experts presented the possibility that early detection or prevention focused around the fallopian tubes might allow women to temporarily delay BSO until closer to natural menopause. But medical experts need evidence that it is safe and effective before they can recommend salpingectomy (removal of the fallopian tubes) as a risk-reducing option. This requires a research study comparing outcomes of women who have salpingectomy, women who have BSO, and those who choose surveillance. The design of such a study faces several challenges. A big concern has been whether or not high-risk women would be willing to participate in a prevention study examining fallopian tube removal followed by removal of the ovaries later.

To answer this question, in 2011 FORCE conducted a survey on attitudes of high-risk women towards participating in ovarian cancer risk-reduction research. Preliminary results were presented at our 2011 annual conference and shared on our blog. Almost one-third of the 333 respondents would consider participating in a prophylactic salpingectomy study. We shared this finding with the research community as evidence that a salpingectomy study would be feasible and that women would enroll in such a study.

At our 2012 conference, gynecologic oncology experts Dr. Illana Cass and Dr. Douglas Levine presented the pros and cons of further research on salpingectomy to lower the risk in high-risk women.  The presentation used a debate format and presented two sides of the salpingectomy issue:

Arguments against developing a salpingectomy study included:

• Although many cancers in high-risk women may start in the fallopian tube, we have no proof that all ovarian cancers begin in the tubes.
• The benefits of salpingectomy are unknown and likely less substantial than BSO.  The surgery is unlikely to impact breast cancer risk. Meanwhile, there are well-documented benefits of BSO for mutation carriers.
• Many experts are concerned that women who undergo surgery to remove only the fallopian tubes will not return for additional surgery to remove their ovaries after they undergo natural menopause.
• Designing such a study would require a large, costly, cooperative research effort that would take over a decade, thousands of high-risk women participating, and massive recruitment and follow-up effort.

Despite these valid concerns, there were strong arguments presented in favor of studying salpingectomy as a risk-reducing option for high-risk women, including:

• Salpingectomy might serve as an “interval surgery” to manage and lower risk in high-risk women who are not ready for BSO and would otherwise opt for surveillance only.
• Women who undergo salpingectomy can maintain their ovaries longer and avoid long-term medical consequences of surgical menopause.
• This type of large-scale research would provide valuable information about development, prevention, and treatment of ovarian cancer for women with BRCA mutations and those without.

Both presenters at our conference agreed on one important conclusion: the time is right for additional research on salpingectomy.

Fortunately, other medical experts agree. During the Gynecologic Oncology Group meeting this January, the Cancer Prevention and Control Committee approved further development of a concept to design a feasibility study of risk-reducing salpingectomy. Many proponents, including the National Cancer Institute’s Division of Cancer Prevention and FORCE enthusiastically endorsed designing such a study. It’s important to note that despite this progress, it still may be more than a year before a salpingectomy study would open at GOG sites around the country.

We know that these studies are needed and that many high-risk women would consider participating in them. As with the development of new PARP Inhibitor research studies (which I blogged about last week), I feel optimistic about salpingectomy studies moving forward and proud of FORCE’s hard work and contributions in promoting these studies. The voice of the hereditary breast and ovarian cancer community has been heard. Our community is highly motivated to participate in hereditary cancer research and once the study is developed and open, I feel confident that women will enroll. Please stay tuned for further updates. To read more about fallopian tube and salpingectomy research, read our Research Updates article and view our on-demand webinar on this topic.

Drawing Attention To High-risk Screening

Reports are everywhere in the media about which celebrities underwent prophylactic mastectomy, the difficulty of their decision, and why these women made the choice. These media reports can be helpful to our community as they raise awareness of hereditary cancer risk and risk-management and remove the stigma of mastectomy. However, given the media focus on mastectomy, it would be easy to assume that surgery is the only option for high-risk women, when in fact, there are several options available to women who are at increased risk for breast cancer. When the media focuses solely on surgical risk-management, they may inadvertently send a message that this the only way to manage increased risk for breast cancer. Some women may avoid seeking information about their risk for fear that their only recourse will be surgery.

Risk is a spectrum. We know how to identify individuals in the highest risk category for breast cancer—women with a BRCA1 or BRCA2 mutation face some of the highest known lifetime risks for cancer, as high as 85% compared to 12.5% for women of average risk. Other gene mutations are also linked with a high risk for breast cancer, including Cowden Syndrome that is associated with a mutation in the PTEN gene, and Li Fraumeni that is associated with a mutation in the P53 gene. Like women with BRCA mutations, women with these other mutations face a high lifetime risk that is usually younger at onset and can be associated with a more aggressive cancer.  Continued media attention highlighting genetic counseling and appropriate use of genetic testing can be life-saving. For example, a recent publication estimated that less than 10% of women with a BRCA mutation are aware of their risk.

Current expert guidelines recommend several risk-management strategies for high-risk women with these mutations. National guidelines for breast screening in women with BRCA mutation include annual MRI and mammogram beginning at age 25 or 10 years earlier than the youngest cancer in the family. Surveillance may also be coupled with pharmacoprevention; usually tamoxifen, which has FDA approval for use to lower risk of breast cancer in high-risk women. High-risk surveillance has been shown by research to find cancers earlier when they are more treatable. But surveillance is not infallible, and we know that for some women, the cancer will not be found until it has spread outside the breast and lymph nodes. Therefore, the national guidelines also support the discussion of prophylactic or risk-reducing surgery. Although drastic, it is the most effective means for lowering the risk for breast cancer in high-risk women. Surgery is not for everyone, and surveillance is considered by health care experts to be a viable option for high-risk women to manage their breast cancer risk. Research has shown that risk-reducing mastectomy does not improve overall survival – even in women who are at very high risk – although other outcomes may be more important to women, including avoiding a cancer diagnosis or the consequences of treatments such as chemotherapy, radiation, and axillary dissection.

Genetics research is improving our ability to pinpoint risk along the risk spectrum. We can now better identify women who are of moderately increased risk. Emerging panels are looking for changes in multiple genes beyond BRCA, PTEN, and P53 that may increase a woman’s risk for breast cancer that confer an “intermediate-risk” of about 20% or higher lifetime risk for breast cancer. Women with a strong family history of breast cancer with no identified cancer mutation also fit this category. Experts have guidelines for women of intermediate breast cancer risk. The American Cancer Society recommends that women with a 20% or higher lifetime risk for breast cancer undergo annual breast MRI in addition to mammograms, starting at a younger age. Other known risk factors may influence women’s risk management decisions, including having very dense breasts that are hard to image or prior abnormal changes on a biopsy, such as atypia or LCIS.

Most women with higher-than-average risk for breast cancer begin with surveillance. Some may ultimately choose to undergo risk-reducing surgery later based on new information, abnormal biopsies, or other factors.

A lot of misinformation and misunderstanding still surrounds breast cancer screening, and women undergoing breast surveillance need credible information and peer support. Some health care providers continue to tell women that they are too young or do not need mammograms or MRI. And research is ongoing with new studies looking at ways to improve breast cancer detection in high-risk women. Medications such as metformin are being investigated for lowering risk of breast cancer. Like all aspects of living with increased cancer risk, some aspects of surveillance differentiate and isolate women from their average-risk peers.  By building a strong and unified community, educating women, providing peer support, and advocating for more research and better options, FORCE will continue to provide needed resources for this portion of our community. The stories may not be as exciting or as compelling to the media as those about prophylactic mastectomy, but we must also continue to remind the media that many options are available for women who are at increased risk for breast cancer, and emphasize the importance of consulting with genetics experts to receive credible, personalized information prior to making any risk-management decisions.