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.

Thoughts on Turning 50: Transformations

For many people, turning 50 is an unappreciated milestone that they would rather not acknowledge, but I feel differently. Some people find themselves going through a midlife crisis; me, I’m facing 50 by signing up and training for my first marathon!

Like most of us I’ve undergone many transformations in my life. Some have been intentional while others resulted from circumstances beyond my control. Recently while

at 26 I was neither fit nor happy

looking for old photos, I ran across some pictures of myself when I was in my 20s and 30s. I was not fit then, and I didn’t resemble the person I am now. At 50 I am the healthiest, most physically active, and most content that I have ever been in my life. Many people who have known me only in the last few years have commented that they can’t imagine me when I was not active, energetic, and happy. So running across photos of a younger me was a sobering reminder of the effort and motivation that it took for me to be where I am today.

Much of my motivation for becoming more fit was my breast cancer diagnosis at age 33 and a recurrence the following year. Both prompted me to advocate for myself and do everything I could to improve my chances of survival (increasingly, research validates the benefit of a healthy diet and active lifestyle for surviving cancer). My other motivation was my family. I lost my mother at a young age. Her weight and lack of fitness contributed to her young demise. I was determined not to repeat the same mistake; I wanted to be around as long as possible for my son!

Transforming myself to a marathon runner won’t be easy, but I’ve faced harder challenges and become stronger because of them. My most difficult transition came when I was diagnosed with breast cancer at age 33. All my life cancer had been a subject avoided or treated with dread. As I went through treatment I felt the stigma and isolation of cancer. Strangers approached me when I was out with my son, my face without eyebrows or lashes, my head without hair wrapped with a scarf that tipped them off that I was someone with cancer.  Some people offered advice or encouragement, but others treated me with pity. I didn’t like this negative attention, which left me feeling uncomfortable and devalued.

Almost as difficult was the transition to my post-cancer life. Even after treatment ended, I felt different from my friends and peers. Dealing with uncertainty about my future and post-treatment depression, I didn’t feel like I had anything to offer them. The transformation that allowed me to re-enter life, find a “new normal,” and make new friends post-cancer didn’t happen overnight. It was almost a decade before I was emotionally ready to make friends outside of the cancer survivor and previvor community.

Advocating for the HBOC community became more important and rewarding than being a vet.

My transformation from veterinarian to patient advocate was also gradual and not entirely voluntary. I wanted to be a veterinarian for as long as I can remember. Once I achieved my dream, I loved my practice and the work. I loved helping animals and people. But my motivation for founding FORCE and transitioning to director was more powerful than my love of veterinary medicine. There were many great practicing veterinarians but there was only one organization devoted to hereditary breast and ovarian cancer. My own isolation, confusion, and loneliness during my hereditary cancer journey led me to found FORCE so no one else would have to face the hereditary cancer journey alone.

Now at age 50 I’m in the best shape of my life and ready to take on a new challenge!

Now, as a 50-year-old—an age I never thought I would reach—I am ready to face a new challenge: entering the Marine Corps Marathon. My motivation is two-fold. Although I now love exercise and being fit, the demands of a marathon reach beyond fitness. It also requires commitment, discipline, perseverance, endurance, and focus. Training to run a marathon at age 50 is my way of choosing how I transition to middle age and being able to face the next half-century on my own terms. My other motivation is to benefit the community and organization that I have dedicated my life to serving. I hope that my marathon quest motivates others to try to achieve their goals. And importantly, I hope to raise funds for FORCE and encourage others to sign up for Team FORCE for the Marine Corps Marathon.

I am not a natural athlete; the photo of a younger me confirms this. If after a half-century this formerly sedentary survivor can transform herself into an athlete, anyone can do the same. I hope my efforts inspire others to pick their own goals, find their personal motivation, and pursue their own transformation.

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.

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.

Progress in Hereditary Cancer Treatment Research

Recently I participated in the Gynecologic Oncology Group (GOG) semi-annual meeting in San Diego. The GOG is part of the National Cancer Institute’s Clinical Trials Cooperative Group Program, whose role is to promote and support clinical trials for cancers. As one of the members of the Patient Advocacy Committee of GOG I participate by providing the consumer perspective and input into the research, assisting with clinical trial recruitment efforts, and disseminating the information from GOG research back to the community.

At the meeting, a research update on the study GOG 280 gave me great hope for better options for our community. I learned that this phase II study examining the PARP inhibitor Veliparib (Abbvie) to treat ovarian, fallopian tube, and primary peritoneal cancer met its enrollment goals. This means that researchers successfully recruited all the study volunteers they needed to determine the safety and explore the efficacy of the drug for treating women with ovarian-type cancers.

Women in the study received oral Veliparib as a “single agent,” which means that the study did not combine the drug with chemotherapy. This study was open only to women with BRCA1 or BRCA2 mutations who had been diagnosed with ovarian, fallopian tube, or primary peritoneal cancer that had recurred after treatment.

This study was phase II: it was a very small, with only about 50 participants. We expect a report of the study results at the American Society of Clinical Oncology (ASCO) meeting in Chicago this spring. We are hopeful that the results will be positive and will pave the way for a larger, phase III Veliparib study that would be open to hundreds of ovarian, fallopian tube, and primary peritoneal cancer patients. Stay tuned to FORCE for updates on the research results.

Although the ovarian study is filled, there are other open PARP inhibitor studies, including a large phase II study looking at PARP inhibitors in combination with chemotherapy for advanced hereditary breast cancer which is open and has been expanded to many sites across the United States and internationally. Other smaller PARP inhibitor studies, including studies for women with ovarian cancer, and a study for women with early stage breast cancer who have residual cancer after neoadjuvant chemotherapy are open or will be opening soon.

I need to acknowledge all the brave volunteers who enroll in any medical research, and particularly thank those who participate in hereditary cancer research. Your participation is critical for progress in cancer prevention and treatment and gives us all hope for better options for us and for future generations.

Visit the Clinical Trials and Research Section of the website for more information and our Featured Studies Page for links to open PARP inhibitor and other studies. We will be presenting a free webinar: Updates on PARP Inhibitor Research on February 28. Visit our Be Empowered Webinar page to register or for more information.

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.

Clinical Trials for Hereditary Cancer: Where the Rubber Meets the Road

This blog is a call to action! Please read on, and then post, blog, tweet, retweet, and share about this issue so that we can assure that hereditary cancer research continues!

The call for more research is a constant theme for all diseases including cancer, and sometimes it’s easy to get frustrated by the slow pace of progress. The multistep process from discovery to FDA approval is often long and doesn’t always end in success. But research is necessary to assure that new treatments work as well or better than current standard-of-care. For this to happen, studies must recruit enough people to prove that the agents work. This is particularly critical for research that focuses on a small specific population like people with a BRCA mutation.

PARP inhibitor research is a prime example. I first heard about PARP inhibitors at the 2005 ASCO annual meeting. In her plenary address on advances in hereditary cancer, Dr. Barbara Weber from the University of Pennsylvania mentioned targeted agents (PARP inhibitors) that were designed to exploit weaknesses of cancer cells in people with BRCA mutations. This was exciting news! I was hopeful that this could be the beginning of personalized therapy for people in our community. From that moment on, I vowed to do whatever it took to learn about, share with our community, and promote the studies to determine whether these drugs worked.

Early small clinical trials of PARP inhibitors were promising, but delays and road-blocks affected development of larger research studies. Some of the roadblocks had to do with study design; others involved dosing or side effects as researchers determined the most effective combinations of PARP inhibitors with other anticancer agents. Despite these issues, enthusiasm continues for the potential of these drugs in people with BRCA mutations. Yet, eight years later, there are still no FDA-approved PARP inhibitors and people are still dying of hereditary cancers!

FORCE has continued to advocate for further research on PARP inhibitors, petitioning scientists, the FDA, and pharmaceutical companies to address the road-blocks and challenges and to facilitate the research and find answers for hereditary cancer. After eight long years, our pleas and efforts have been rewarded. Several PARP inhibitor studies are now recruiting, including a large, Phase II study on PARP inhibitors for women with BRCA-associated advanced breast cancer. Our participation in this research is critical. Unless enough people participate, these studies will not continue. If enrollment falls short, the next time scientists have an idea for treating or preventing hereditary cancer, they may decide that the BRCA community is too difficult to research, and fewer studies will be designed for us. That would be tragic considering how many members of our community develop and succumb to cancer.

This is where the rubber meets the road!

We have worked long and tirelessly to advocate for this research. Now that we have it, we cannot afford to turn a deaf ear. At this moment, the fate of hereditary cancer treatment research rests with each of us. Although most of the current studies are open only to women with advanced cancer, even if that doesn’t describe you, perhaps you know someone who fits that description. If PARP inhibitors work for advanced hereditary cancer, the next step will be tests to see if they also work for earlier cancers.

Here is what you can do to help:

• Get involved. Consider enrolling in a study if you are eligible, and share information about PARP inhibitor research with everyone that you know. Post it prominently on your social media pages, share it with your online or in-person support group, discuss it with your local media, and write or blog about why hereditary cancer research is important. Please remember to share your efforts with us. Email us,  post on FB or the FORCE message boards about ways you have spread the word about this important research.
• Stay tuned to FORCE to learn of new available studies. We will be updating this page in the upcoming weeks with new featured studies so check back often.
• Support FORCE with a donation to help us continue our important work to advocate and recruit for research specific to hereditary cancer

We must participate in and promote hereditary cancer clinical trials and other studies if we and future generations are to realize more effective treatment and prevention for hereditary cancers.

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.

13 Things About Breast Reconstruction

A guest blog by Kathy Steligo

Although many women choose to forego breast reconstruction, it is almost always an option after mastectomy. Research shows that reconstruction can improve psychological well-being and quality of life, and result in improved body image and self-esteem. Most women are not informed about breast reconstruction before their mastectomy, however, so it pays to do your homework to discover and understand the benefits and limitation of all your alternatives.

Breast reconstruction is a topic of interest to our community, because so many of us face mastectomy to either treat or prevent breast cancer. So we’re very happy to bring you this month’s blog. In keeping with our 2012 “13 Things” theme, we present 13 informational tidbits about reconstruction.

We also recommend two new publications to help with your decision-making process. Our new Show & Tell book includes photos and personal comments from FORCE members who have had reconstruction. And the long-awaited 3^rd edition of The Breast Reconstruction Guidebook hit the streets on November 8 (you can review the Table of Contents on the link above). The FORCE Post Mastectomy Photo Gallery is another resource for viewing post-mastectomy photos (and uploading your own photos to share with others).

1. New breasts can be reconstructed at any time following mastectomy, even years later, but there are definite cosmetic advantages to immediate reconstruction that is performed simultaneously with mastectomy. Immediate procedures allow for minimized mastectomy incisions that are made to facilitate reconstruction.
2. Reconstruction doesn’t restore sensation that is lost when tissue is removed during mastectomy. Most women have very little sensation in their reconstructed breasts. Much of the area remains permanently numb, although minimal feeling does return as some nerves regenerate. Generally, some feeling is recovered in the upper portion or outer perimeter of the breast in the areas that are farthest from the mastectomy incision. Nor do reconstructed nipples have sensation or response. Although they look quite real, they lack nerves that produce feeling in the skin. Women with tissue flaps often regain more feeling than women with implants, because the fine nerves in the flaps regrow once they are transferred to the chest.
3. Many women are candidates for nipple-sparing or areola-sparing mastectomies, which require a breast surgeon who is experienced with these procedures. (Cancer originating in the nipple is rare; most women’s nipples do not include the intraductal infrastructure that supports formation of breast cancer cells.) Healthy nipples on reconstructed breasts don’t always retain natural sensation, because much of the underlying nerve system is destroyed when breast tissue is removed. Areola-sparing mastectomies remove the nipple but preserve the pigmented skin surrounding it.
4. Independent review of hundreds of scientific papers has identified no proven link between implants and systemic disease or autoimmune disorders.
5. Physicians cannot predict which women will have problems with implants, but having radiation therapy compromises blood flow to the skin, which increases the likelihood of capsular contracture and other problematic issues.
6. Implants remain the same size over time, while breasts rebuilt with your own tissue change according to fluctuations in your weight.
7. Some surgeons use hybrid expander-implants that are gradually filled with saline. When the desired size is reached, the fill valve is sealed and the expander-implant is left in place. No exchange surgery is required.
8. Plastic surgeons who perform traditional expander-to-implant surgery and attached tissue flap procedures that use skin, fat, and muscle are more common (and easier to find) than surgeons who provide direct-to-implant and muscle-sparing flap procedures.
9. Although they are still in the minority, more surgeons are performing muscle-sparing breast reconstruction procedures.
10. Expander-to-implant reconstruction requires a shorter surgery than a tissue flap operation, but the overall timeline is longer.
11. Fat grafting—liposuctioning fat from the body and transferring it to the new breast—is often used to improve symmetry, contour and other cosmetic defects. The process isn’t always completely successful, however, and often 50% of more of the transplanted fat is resorbed by the body. New methods of fat grafting may offer intriguing possibilities, keeping a greater percentage of transferred fat in the breast, and even building new breasts without surgery, but much more study is needed.
12. You can “train” for surgery. Being in the best possible physical condition will help your body weather surgery and recovery. You don’t have to attain the level of a professional athlete, but anything you do to strengthen your cardiovascular system and body will help you get back to your normal routine. If you smoke, you must refrain from doing so for at least three weeks before and after your surgery (maybe it will be the impetus you need to quit for good!) Smoking restricts blood flow throughout the body and can potentially compromise any surgery. It is particularly troublesome with flap reconstruction, because a portion or all of the new breast can die without a robust blood supply.
13. The Women’s Health and Cancer Rights Act of 1998 requires group health plans that cover mastectomy to also pay for breast reconstruction, including procedures that are required to attain symmetry or to address complications. The law, however, does not stipulate specific surgeons, hospitals or procedures. That is left to the terms of the health insurance policy.