Increased Awareness Leads to Accelerated Research

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

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

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

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

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

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

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

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

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.

Every Story Matters

Since Angelina Jolie recently shared her personal experience with genetic testing and prophylactic surgery in the New York Times, public awareness of hereditary cancer is at an all-time high. The media surrounding Ms. Jolie’s revelations has also provided unparalleled opportunities for members of the HBOC community to share their personal accounts as well.

How did you learn about hereditary cancer? Was it a chance meeting with someone who was high risk? A brochure? A TV health show? For me, it was a magazine article I read back in 1997. When I was diagnosed with breast cancer at age 33, my doctors recommended a single mastectomy on one side, but they never told me about genetic counseling or testing, despite my having several red flags for a hereditary syndrome: young onset breast cancer, Jewish background, and a paternal grandmother who died young of abdominal cancer. I certainly would have made different surgical choices if I had known I carried a mutation. The article motivated me to pursue genetic counseling and testing, and ultimately, I chose prophylactic surgery, which discovered early cancer in my healthy breast.

All of our stories are important. Each story we share and every article about HBOC raises awareness and provides an opportunity for someone to recognize himself or herself in the writing and to pursue genetic counseling, testing, and risk-management options.

In a brilliant example of how awareness can save lives, reporter Stacey Sager first shared her hereditary cancer story on WABC-TV in New York in October 2011. Stacey was on a campaign to raise awareness and save lives. A 13-year breast cancer survivor at the time, Stacey had undergone testing for BRCA and found that she carried a BRCA1 mutation. Testing and BSO saved her life. As Stacey bravely allowed cameras to document her BSO, early precancerous changes were found in her fallopian tubes. (Ovarian cancer is rarely found early, other than during prophylactic surgery.) When Stacey wrote a guest blog for Thoughts from FORCE, a reader responded with the following comment, “For years my doctors have been trying to get me to take the BRCA testing because of my family cancer history, but I simply was not ready. After watching your televised story I went to the doctor the next week for my BRCA test.”

Stacey’s story resonated with and motivated more than one person. Celebrity singer/songwriter Kara DioGuardi happened to catch Stacey’s story while in New York City while she was appearing in the Broadway production of Chicago. Kara, who was interviewed by People magazine, shared that a chance viewing of Stacey’s story changed her life. Kara knew about her family history of cancer, but she didn’t know about BRCA testing until that crystalizing moment. When she returned to L.A., she immediately sought care for genetic testing, and then underwent BSO. A dear friend who agreed to be a surrogate for Kara and her husband was implanted with Kara’s last remaining embryo from prior IVF and carried their baby to term; little Greyson is now 3 months old. Kara shares more of her story in a moving interview where she gets to meet Stacey in person and thanks her for publicly sharing her story and possibly saving her life.

Experts estimate that less than 10% of the almost 1 million people in the United States with a mutation are aware of their high-risk status. We know that risk assessment and intervention can improve survival for high-risk individuals. But people cannot take action if they are unaware of their risk. It is up to us to raise the profile of HBOC until every person has access to the tools, information, and health care experts to assess their risk, and every high-risk person has the education, support, and resources they need to make informed decisions about their risk.

In her Voices of FORCE account for our Joining FORCEs newsletter, member Lita Poehlman shared how a chance meeting with a FORCE member led her to genetic counseling and testing, and subsequent prophylactic surgery discovered precancerous changes. She credits that chance meeting with saving her life. These personal anecdotes remind us that every act of sharing is significant and every story matters!

Other publications share accounts from the HBOC community, including several  memoirs: Previvors, Pretty Is What Changes, What We Have, Apron Strings, Beyond the Pink Moon, and Pink Moon Lovelies. The documentary In the Family (which is available for free viewing online until May 26) follows the intimate story of filmmaker Joanna Rudnick and several families facing hereditary cancer. Our community blog page has links to the HBOC  blogosphere, and the Voices of FORCE section of the website is filled with your stories. You can add your story and voice to our pages. Writing and sharing your accounts raises awareness about the impact that hereditary cancer has on everyday people, inspires others to learn more, engenders compassion and understanding for our community, and saves lives.

Proposed Guidelines on BRCA Testing Leave Many Gaps

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

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

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

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

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

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

FORCE Concerns with the Draft Guidelines

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

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

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

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

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

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

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

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

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

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

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

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

Gene Discovery, Patents, and the Community

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

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

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

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

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

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

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

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

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

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

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.

Weighing the Risks and Benefits of Screening Mammography

Two recent research articles have questioned the value of mammograms and opened up a dialogue about possible benefits and harms of screening for breast cancer. One study looked at mammography in the general population and the other in high-risk young women. Both studies raise interesting concerns, but neither provides the definitive answers needed to dismiss mammography as a screening tool.

The first article looked at large population-based statistics over three decades and concluded that although mammograms found more early cancers, they did not lead to a similar reduction in cancers diagnosed at a late stage. The authors conclude that screening mammograms are leading to the overdiagnosis and treatment of a substantial number of women. Based on these conclusions, the authors question the benefit of screening mammograms for the general population.

Our review of the research and conclusions of this article can be viewed here. Some of our concerns are:

• The study combines DCIS (a type of non-invasive cancer) and stage I breast cancer in the same category as “early-stage” breast cancer even though stage I breast cancer behaves differently than DCIS.
• The study was not designed to distinguish women by age or outcome.
• The authors imply that earlier diagnosis equals overtreatment. However, there are tests available that look at tumor samples to better determine which early-stage cancers are more likely to behave aggressively and which women would benefit from further treatment. If we don’t find these early cancers through screening then we lose an opportunity to tell which ones are more likely to become advanced.
• Changing screening practices to lower the number of women that are overdiagnosed could lead to an increase in women being diagnosed at a stage requiring more extensive treatment.

In an emotionally-charged opinion piece in the New York Times entitled “Cancer Survivor or Victim of Overdiagnosis?” one of the study authors made these recommendations:

“We must redesign screening protocols to reduce overdiagnosis or stop population-wide screening completely. Screening could be targeted instead to those at the highest risk of dying from breast cancer—women with strong family histories or genetic predispositions to the disease. These are the women who are most likely to benefit and least likely to be overdiagnosed.”

Personalizing screening recommendations based on risk makes sense. Unfortunately, the health care community doesn’t always use the risk-assessment tools available to help identify women in the highest risk category. Many women with BRCA mutations do not learn that they are high risk until they are diagnosed with breast cancer, often based on a screening mammogram. Changing screening guidelines will disproportionately hurt these women in our community.

The author also suggests:

“What should be done? First and foremost, tell the truth: women really do have a choice. While no one can dismiss the possibility that screening may help a tiny number of women, there’s no doubt that it leads many, many more to be treated for breast cancer unnecessarily. Women have to decide for themselves about the benefit and harms.” 

As someone on the receiving end of a mammogram call-back, and ultimately, a breast cancer diagnosis, I understand how anxiety-provoking screening and biopsies can be. Relaying to women the possible consequences if their screening finds an abnormality is critical. A balanced discussion should also include information about the possible consequences of a delayed diagnosis, the additional treatment that might be required for later-stage diagnosis, and the existence of decision-support tools such as Oncotype DX and Mammaprint and other technologies that can help determine which early stage cancers, once found, are more likely to behave aggressively.

The author goes on to state the following:

“But health care providers can also do better. They can look less hard for tiny cancers and precancers and put more effort into differentiating between consequential and inconsequential cancers.”

Research is ongoing to determine which cancers are more or less likely to behave aggressively. Currently we do have the technology to test breast tumors for markers of aggressive behavior. But these tests require detecting the tumors and sampling them through biopsy. I strenuously disagree with his suggestion that doctors “…look less hard for tiny cancers and precancers…”  and the assertion that diagnosing breast cancer at early stages equates to overdiagnosis and treatment. If we pass up the opportunity to find these abnormalities with mammograms and biopsy, we deprive women of critical information on which to base their health care decisions.

A second study raised interest and alarm about mammograms in high-risk women younger than age 30.  In this study researchers concluded that exposure to ionizing radiation before the age of 30 is associated with an increased risk of breast cancer. Closer review of this second article, however, highlights areas that warrant more examination before we eliminate mammograms as screening tools for young previvors. Questons have also been raised about this study’s design and conclusions. (You can read our full review of the study here.) Some of the concerns include:

• The increased breast cancer incidence when comparing those with no radiation exposure to those with any exposure between ages 20-39 was not statistically significant.
• The estimated radiation doses used in this paper were self-reported and therefore subject to “recall bias.”
• Although MRIs are very sensitive for finding abnormalities in the breast, mammograms find microcalcifications, small changes that can indicate an early cancer which are sometimes missed by MRIs. There is concern that in eliminating mammograms, some of early cancers might be missed until they are more advanced.

Members of the FORCE Scientific Advisory Board agree that the current study addresses a critical question that must be answered, but generally feel that the results of the current study are not conclusive. More research is needed to clarify the possible link between radiation exposure and increased cancer risk in BRCA1/2 carriers; expert panels will continue to update screening guidelines based on those future results.

Although imperfect, mammography does save lives, and we must apply all the means we have to save as many lives as we can.  More research is needed to determine if the harms of diagnosis and treatment outweigh the consequences of missing cancers, and to provide a clearer understanding of how many more lives will be lost if guidelines are changed to remove the recommendation of screening mammography. If policy-makers choose a shared decision-making strategy for breast screening, all factors must be shared with each woman to help her make her own informed decision. In order to maximize breast cancer outcomes, the health care community needs to assure that women have access to qualified experts who can help assess their risk for breast cancer. For high-risk women, experts concur that the benefits of screening with mammograms and MRI outweigh the risks.

A Public Response to Dr. Ivan Oransky

To put this post in context, I was forwarded the link to this webcast from the recent TedMed Conference. I suggest watching this presentation by Dr. Ivan Oransky prior to reading the following blog.

Dear Dr. Oransky,

I recently watched your TedMed presentation and I share your concerns about medical overtreatment of certain conditions and the importance of weighing risk and harm when considering medical interventions. I agree with your point that not all medical tests and interventions have clinical value. I also agree that all stakeholders should share the responsibility for appropriately applying medical technology based on evidence and outcomes. However, I disagree with some of your statements, and I feel compelled to correct what I believe is a misunderstanding on your part about the term “previvor,” and the intent of the advocacy group FORCE in coining and using the term.

In my opinion, your assertion that advocacy groups use “previvor” to make more people feel they are at risk and raise more funds is incorrect. I founded FORCE in 1999, not to make money, but to ensure that people have access to credible information about hereditary cancer, that hereditary cancer research continues to provide better options, and that no one must face it alone. FORCE does not inflate people’s risk. We refer people to genetics experts based on professional consensus guidelines published by the National Comprehensive Cancer Network (NCCN).

Further, previvor is a term developed for a group of people who carry a mutation that confers a high cancer risk in their lifetime. FORCE is a national non-profit organization with a mission to serve individuals and families with a BRCA gene mutation or hereditary cancer. We coined the term to refer to individuals who are genetically predisposed to cancer but have not been diagnosed. The term was a response to a plea by one of our members who lost her mother to cancer at a young age. Learning that she had inherited a BRCA1 mutation and potentially faced the same fate, she sacrificed her own breasts, ovaries, and fertility to reduce her very high risk. Yet she felt dismissed and marginalized by people who did not understand her situation.  She articulated what many in our community felt: they needed and wanted a way to collectively organize, support each other, and advocate for resources to address their unmet needs.

My own breast cancer was diagnosed at age 33 and recurred the year following my initial treatment. I endured chemotherapy, radiation, and an increased likelihood of an early death from cancer. My son was only two years old at the time. I was forced to take a leave of absence from my work during treatment and went into medical debt to pay hospital and treatment costs. Had I known of my inherited predisposition at the time I would have taken steps to avoid cancer or detect it earlier. My experience is just one illustration of the financial, emotional, and physical costs of not knowing about a genetic predisposition to disease. These burdens impact entire families and can affect long-term quality of life. Many women pay with their lives.

Too many hereditary cancer families have watched their loved ones battle and too often lose their lives to the disease. They want to know what they can do to avoid the same fate for themselves and their own children. They face lifetime risks for cancer as high as 90%. Their risk-management options—preemptive surgery, risk-reducing medications, and heightened surveillance—are not without side effects or other risks. complex information about risk and risk-management and using it to make informed decisions. Although risk-management options are not ideal, most genetics professionals concur that hereditary cancer risk assessment and associated interventions have clinical utility. Research from peer-reviewed journals demonstrates that risk-management options can lower cancer-associated and overall mortality in the highest-risk cohort.

As an organization whose mission includes education, FORCE understands the challenges of presenting complex information in a balanced, understandable, compelling, and humane fashion. We take this responsibility seriously and we frequently consult with our expert advisory board for guidance. It is my opinion that your representation of previvors and our advocacy for the community was neither balanced nor accurate. Your baseball analogy illustrated your point about overtreatment of pre-conditions, but you neglected to mention inherited cancer risk, the situation for which the term was established. You cited “pre-acne” as an example of the absurdity of treating a precondition, even though the consequences of a diagnosis of acne and a diagnosis of cancer are not remotely the same. Women with BRCA mutations have elevated lifetime risk of developing breast and ovarian cancer that is many times higher than the general population. They are more likely to develop aggressive cancers and at a younger age when they are less likely to be screened. Thousands of women die from these cancers annually. Given these facts, the example of pre-acne is not a realistic comparison to inherited cancer risk and in my opinion insults a group of people with a very serious set of medical concerns.

Members of our community have an inherited mutation that leads to changes on a cellular level, which put them at very high risk for disease. Although our genetic differences may not be obvious on the surface they cause challenges that separate us from other people who do not possess these mutations. Ignorance and ridicule directed at people with medical challenges of any type are inappropriate.

I hope that you will provide a clarification of your statements about the meaning of the word previvor to include the fact that it was coined to describe and empower a specific group of people at very high risk for a deadly disease like cancer. Further, I encourage you to use your role as an experienced medical journalist and professor to delve more deeply into the difficult issues of people with BRCA mutations. In doing so you have the potential to make a positive impact on a lot of people.

I am not a baseball player, Mr. Oransky, but I do play tennis. In tennis when you do not swing at the ball, you lose the point. People with a BRCA or other inherited cancer-predisposing mutation face extraordinary risk for a disease that is too often fatal. Many of us have lost so much to cancer. Not swinging at a disease that has a high likelihood of coming our way is not a wise option.

Holiday Guest Blog: Joanna Rudnick

FORCE member Joanna Rudnick, producer of the documentary In the Family  wrote the following special holiday blog.

Of Holiday Miracles and Possibilities

by Joanna Rudnick

This time of year is all about the great miracles and the infinite possibilities.

For most of us, miracle and possibility are the last words that come to mind when we get a positive test result for a BRCA mutation. At least they were for me. (I can think of a number of other choice words that I uttered, many of which are not appropriate to write here.)

Grieving for all that I immediately wrote off – health, happiness, future, motherhood, love – I failed to realize that I was sitting on top of a heap of little miracles that would alter the course of my life and make the impossible…possible.

From “coming out” and feeling up my first pair of breasts on camera to the birth of my baby girl, this crazy, unexpected, grueling, electrifying, terrifyingly, humorous, humbling, raw and beautiful road was paved with tiny miracles:

Miracle #1: Dr. Mary-Claire King – how lucky are we that this brilliant scientific mind, fueled by the incomprehensible loss of a childhood friend to cancer, dedicated her life’s work to tracing the familial link for breast cancer down to the molecular level. Picture the countless late nights she spent pouring over pedigrees that stretched the length of the floor in her lab and beyond to get us where we are now.

Miracle #2: Our mothers, fathers, sisters, brothers, grandmothers, grandfathers, great-grandmothers, great- grandfathers, aunts, uncles, great aunts, great uncles and cousins, who left us their health histories  - our most valuable clues – so that the next generations would not suffer in silence with the disease that cut too many of their lives far to short.  

Miracle #3: FORCE! Thirteen Years ago, Sue Friedman had the chutzpah and dedication to leave her successful career as a veterinarian to create a home for all of us. Her one-person-machine turned into thousands of families from around the world coming together to share information and offer support and encouragement to each other.  (Miracle #3A: Sue was the first person I called when I launched In the Family and she immediately jumped on board.)

Miracle #4: in the spirit of true collective action, We came together as a community to fight for protective legislation to prevent health insurers and employers from discriminating against people based on their genes; We supported the ACLU in their challenge to the BRCA patents – a case likely to be heard by the Supreme Court; and We continue to fight against funding cuts for breast and ovarian cancer research.

Miracle #5:  Debbie Wasserman-Schultz – The head of the DNC is not only out about being BRCA+, her breast cancer diagnosis and her surgeries, she is actively fighting in Congress for more research dollars, education and awareness programs.

Miracle #6: The Good News -That we have the ability to find out; that there is surveillance and prevention and that both are getting better (the real miracle will be a reliable blood marker for early detection of ovarian cancer); that we can talk about BRCA and people know what we’re talking about; that fertility options are improving at a rapid pace (although, no more affordable) and reconstructed boobs are getting even hotter; PARP inhibitors; the Affordable Health Care Act (say goodbye to discrimination based on a pre-existing condition); and being part of a community where all of our choices are respected no matter which path we choose.

Miracle #7: The Silver Lining (this one is personal) – The people in my life who got me to see the possibilities (and these are only a few; there are too many to list)– Linda Pedraza, “It’s life and you don’t mess with that”; Martha Haley, the poet warrior; Cookie and Lewis Rudnick, it’s all about family; Jordan, loves me anyway and every way; and Eloise, I can’t put it into words.

Wishing you all happy, healthy and fulfilling holidays.  Here’s to a 2012 full of more miracles in the BRCA world.

Love,

Joanna Rudnick

In honor of the season, please share  your holiday blessings and miracles with us! Happy Holidays!

HBOC Week was a Success: Let’s Sustain Awareness All Year Long

The squeaky wheel gets the grease. We have heard that saying so many times it has probably lost its true meaning. “Breast cancer awareness” and “ovarian cancer awareness” are terms that also can lose meaning over time. What does awareness mean? Does it really help in any way? Can awareness change behaviors? Can it save lives?

Most people are aware of cancer. They know it exists. They know someone who has been touched by it. By contrast, most people are not aware of hereditary cancer, even when it runs in their own family. Some may have heard of it, but the key facts may escape them. When I was diagnosed with breast cancer at age 33, I had a medical background, and I understood that diseases could have hereditary components. But I didn’t associate my own diagnosis and my paternal grandmother’s young demise from abdominal cancer with a genetic predisposition to cancer. I was unaware of genetic counseling and testing until I read a magazine article about HBOC. From the information in the article I recognized that I had several of the indications for a hereditary syndrome. My health care team never realized I fit the criteria for BRCA testing. It was the dawning media awareness about HBOC that helped me learn about my own BRCA 2 mutation. Since founding FORCE I have heard from countless other women that reading a FORCE brochure or an article about one of our members helped them make the connection between what was going on in their family or understand how genetic counseling may be relevant to their situation. Taking it one step further, many of these same women indicated that surgery found breast or fallopian tube changes that likely would have led to cancer. We know from research that risk management options can increase the life span of high-risk women. 

So when we talk about awareness of HBOC saving lives, it is not an abstract concept. This year thanks to your support and efforts, we reached more people than ever during HBOC Week. We had more media attention. Our outreach groups had more events. Our website traffic increased by 26%. Our newsletter mailing list grew by 14%. Attention among government agencies and researchers leads to more focused efforts to address the disproportionate cancer burden our families face. These tangible successes equal lives saved for members of our community.

Here is my top five list of reasons why HBOC awareness is important:

• The single factor associated with the biggest risk for breast cancer is having a BRCA mutation.
• Most people who are very high risk for cancer are unaware of their risks.
• Cancer screening and prevention recommendations for average risk people are inadequate for those with hereditary cancer risk.
• The more people hear about HBOC, the more likely they are to explore their family medical history and seek out genetics professionals.
• Identifying and preventing cancer in high-risk people has been shown to save lives.

Five things you can do to sustain awareness:

• Watch and share our video. “Like” it and post it to your Facebook page.
• Contact your local FORCE outreach group.
• Volunteer to help FORCE. We have lots of opportunities.
• Make a donation to FORCE. Support our research fund initiative.
• Distribute FORCE brochures.

Let’s continue to drive awareness and increase our momentum. We need more successes like this. Share this blog and lets make the next 12 months HBOC year!