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.

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.

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.

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.

A Healing Light From Within

Below are excerpts from our Joining FORCEs conference welcome address and a keynote talk that I recently gave in Chicago.

Fifteen years ago, there was no FORCE. Back then, hereditary cancer was scarier and lonelier than it is today.

When I was first diagnosed with breast cancer at age 33, it was caught early. I was very lucky to have been diagnosed, since I had no family history of breast cancer, and breast cancer was not on my radar. I was very conscientious about my health, and I found a lump on my very first breast self-exam at age 29. The lump was benign, but it was the reason I was having mammograms by age 33, even though I was not considered to be at high risk. My son was almost two, and Dan and I were getting ready to get pregnant again. I went down the list of things you do before getting pregnant: take folic acid, see the dentist, get a mammogram. That mammogram found microcalcification, which led to a biopsy, and then another biopsy that showed very early breast cancer called “ductal carcinoma in situ” or DCIS.  I was fortunate, as I hadn’t needed any further treatment beyond a mastectomy (unilateral), which was recommended because the amount of precancer that was throughout my breast.

I remember attending a Komen Race for the Cure walk three weeks after my mastectomy and looking out into a sea of pink caps and bald heads, and thinking “that isn’t me, my cancer was caught early.” I isolated and insulated myself and kept those other women at arms length, unable and unwilling and too afraid to define myself as someone with cancer. It made me too vulnerable and I didn’t want to be vulnerable.

Nine months later at age 34, my cancer returned in my lymph nodes. I learned that my original health care team had let me down. What they thought was early-stage breast cancer was actually invasive breast cancer that had already spread to my lymph nodes by the time of my mastectomy. Then they let me down a second time by never mentioning hereditary cancer or genetic counseling and testing. Through a chance reading of a magazine article on Hereditary Breast and Ovarian Cancer Syndrome and BRCA mutations, I learned that I carried some of the indications for genetic counseling and BRCA testing. Back then, I didn’t know how to advocate for myself to receive the best care. That lack of knowledge could have cost me my life. When my cancer recurred I knew that I only had one more chance to get it right, and I sought out the best health care experts I could find.

Like the women I saw at that first walk, I lost my hair with chemotherapy.  Suddenly, I was very vulnerable and afraid as I found myself on the other side of the looking glass, the side I had tried to protect myself from through denial and (regretfully) indifference.  While in chemotherapy I traveled to Los Angeles and stayed with a family friend. She was from a generation that didn’t like to talk about cancer. While we were out for a walk, she ran into an acquaintance, who she introduced to me. Right in front of me, nodding at my bald head, she whispered to her friend, “it’s cancer” as if I couldn’t hear her, or as if not saying the words aloud would protect her from it.

It jolted me and hit me, how different I was from the healthy world. I was a young woman with cancer. I knew that there were others like me, but I had never met them. The whispered words made me recoil, I felt diminished, stigmatized, devalued. But I also rebelled against these feelings.

With my genetic testing, that stigma grew. I learned that I had a BRCA2 mutation. Even the word “mutation” seemed alien, invasive, intrusive. How could something so dangerous and damaging be an integral part of me, of my DNA? I had to find a way to redefine and reconcile those aspects of myself in order to move forward in my journey.

I started writing a poem that I dedicated to all the people who were facing that type of stigma. I entitled my poem “Beyond Survival” because for me, surviving wasn’t enough. The poem was about transcending adversity and stigma, and becoming whole. I won’t share the entire poem but here are a few lines:

Beyond Survival

Our hearts flutter but beat strong,

with the will within us to go on.

To not just survive, but to achieve,

to aspire to inspire; to soar, to believe

that we can make a difference.

Shout it emphatically, the sound

of our existence echoes and resounds

ascends and transcends the farthest bluff,

resonates in crevices where ignorance hides

and divides us.

Do not feel devalued, do not cower.

As long as we draw breath, we’re empowered.

Despite these brave words, after finishing treatment, I suffered from depression. I was afraid that my cancer would recur quickly as it had the first time. These were some of the darkest days of my life, even worse than when I was first diagnosed, and when I had my recurrence. My family suffered with me as I didn’t have the energy or engagement in life that my husband and young toddler deserved. I wanted to be well, but I didn’t know how to get there, so I withdrew. I could have easily stayed in that world of sadness and fear, but around that time I purchased my first computer. I reached out via the Internet to others in online cancer forums, and connected with people like myself who slowly drew me out of my sadness and hopelessness and gave me courage to continue on. They inspired me, but equally important, they needed me and leaned on me for inspiration and support. It was from these women that I learned how powerful, healing, and transformative receiving but also giving peer support could be. Although I had not yet started FORCE there was this kernel of thought that my emotional healing from cancer required reaching out to others and knitting a strong community of people who could unite in solidarity and oppose the forces that would diminish us. I wrote this poem for my online support heroes.

cancer, like a vacuum,

was sucking out my joy and hope

enfolding and enclosing me in an envelope

of despair and fear. 

In the distance I saw a steady glow,

heard a chorus growing closer

one light separating into many

descending on me,

a flock of angels

carrying torches, lighting the shadows,

voices singing, arms embracing, wings uplifting me.

I became one with this throng,

a thousand women strong.

In the distance a figure huddles

and shudders in a darkened corner,

we press onward swiftly towards her;

a thousand and one angels

comfort and support our newest member.

From that lonely kernel of thought grew the organization known as FORCE. Little did I know what FORCE would grow to become and mean in my life and the lives of so many. What I did know was that something needed to be done for me and for others to feel less alone! Whisperings in darkened corners are feared. Their shadows are made larger by the lack of light. But from the time of my recurrence on, when I threw off indifference and denial, I understood that if we could shine a spotlight bright on an issue we could remove some of the fear and ignorance, and that together we are so much stronger, braver, and resilient than we are alone. Fourteen years ago I founded FORCE on the principle that no one should face hereditary cancer alone! I was tenacious and passionate in my outreach and advocacy. I did everything I could to make sure that people received the information they needed to make informed medical decisions—information that I was denied when I started my breast cancer journey.

Part of the wonder of FORCE has been the steady growth of our community since then. No matter people’s situation, they are not alone! Our members draw the same strength that I have from belonging to the FORCE community. I believe that each of us carries some type of torch within us, a flame that sparks our passion and helps ignite the passion of others; a flame that we can use to guide other people who are facing darkness and despair. By joining together we have succeeded in illuminating hereditary cancer to create hope for a brighter future for ourselves and for our families.

The Cavalry Has Arrived!

When I founded FORCE in 1999 it was in the early days of BRCA discovery and testing. I had my own BRCA testing in 1998, over a year after my diagnosis with breast cancer, and only after learning about hereditary cancer by reading a magazine article about BRCA. I immediately understood the significance and power of identifying people with genetic predisposition to cancer, with the goal of preventing cancer or detecting it early. But the technology was met with suspicion and alarm by many individuals and groups, even in the face of emerging research that documented the value of identifying those with a BRCA mutation.

I spent a good portion of FORCE’s early years explaining why our community was important. Back then the hereditary cancer community was frequently dismissed or minimized, emphasizing the fact that we were a small subset of a larger whole. Granted, we don’t represent a majority of the cancer community, but we shoulder a disproportionate cancer burden. And because of our extraordinary high risk for cancer and the generational aspects of inherited cancers, HBOC individuals and families are an overburdened and under-resourced community. We require unique research and resources that provide information and evidence-based solutions for the extraordinary issues we face.

We worked hard in those formative years to raise awareness, unite our community, and assure that both survivors and previvors were acknowledged as cancer stakeholders who had a say and a place at the table. We fought for awareness, educated people on the differences between hereditary and sporadic cancer, advocated for better early detection and risk-reduction options, and helped people make informed decisions. Along the way, we were often asked to justify the prophylactic options for risk-management, and even the need for a hereditary cancer advocacy group like FORCE.

As awareness has grown, FORCE has grown, and so has our voice in the cancer community. And yet there are still many areas of unmet needs when it comes to hereditary cancer clinical care and research. Although improvements have been made, current options for prevention, detection, and treatment of hereditary cancer are still inadequate. Too many people are being diagnosed with and succumbing to hereditary cancers, and the path to drug development and FDA approval for example for PARP inhibitors has been glacially slow. After14 years of passionate advocacy and incremental and modest gains, it would be easy to be discouraged. But as many of you know if you read my blogs, I also like to focus on achievements and advancements, and there have been many.

Once in a while, I have had the privilege to witness a landmark event, a game-changer for our community. Last Monday night was such an event. I was honored to be among over 200 people who attended the opening of the new Basser Research Center for BRCA within the Abramson Cancer Center of the University of Pennsylvania. Established through a transformative philanthropic gift from Mindy and Jon Gray, the center is dedicated to the memory of Mindy’s sister, Faith Basser, who succumbed to hereditary ovarian cancer. The center is devoted solely to research and provision of care relevant to BRCA1 and BRCA2. Not a dry eye could be seen as we watched a video that included Faith’s story and how she became the motivation for her family’s endowment. The video also included stories of members of our community, who shared the devastating toll of hereditary cancer on their families. That night, all of us who attended and watched the video, listened to the speakers, and met the Basser Research team understood the center’s clear, overarching message: HOPE. I was witnessing history being made and a new era for the HBOC community.

I was honored to be among over 200 people who attended the opening of the new Basser Research Center for BRCA

Certainly our community will continue to face challenges, hardship, disparity, and unmet needs. But we have champions and a path to a brighter and more optimistic future with the establishment of the first research center dedicated to the pursuit of better detection, prevention, treatment, survivorship, and supportive care for HBOC. As I told Jon and Mindy Gray when I thanked them for this amazing gift to our community, “the cavalry has arrived.”

Previvor Day: A Solemn Celebration

In searching for inspiration for this blog, I went back to the FORCE message boards to remember when and how the previvor movement began.  When I started FORCE, long before the organization and programs grew to the national influence that we are today, we were merely a message board, a way for people in similar situations to connect virtually. The Internet was new to me then, and the ability to reach out to virtual strangers remotely and receive comfort and guidance seemed novel and amazing. When I couldn’t find the support I needed in my immediate vicinity, I could reach out over the miles, type an SOS, and get instant wisdom, advice, and compassion. I could then draw from that support when and where I needed it (and back then I needed it a lot). Over the years many of these “strangers” have been my lifeline and many have become my dear friends. Fourteen years of survivorship later, I still periodically turn to my cyberfamily, but like many who have been part of our community for over a decade, time can sometimes softened the sharp edges of fear, loss, and grief that surrounded my diagnosis, recurrence, genetic testing, and surgeries and my accompanying need for support.

It has been a while since I revisited the archives of our website. With over 300,000 posts in our current database and over 300,000 archived posts, our message boards are the single largest repository of the hereditary cancer experience. These postings are a wealth of wisdom, support, kindness, grief, and gratitude. After 14 years of advocacy, it’s easy to focus on the challenges, the frustrations, and the problems we have yet to solve. So revisiting the past is healthy, and provides me with an opportunity to remember old friends and reflect on my growth and the growth of the organization.   Occasionally I will encounter a post that stops me in my tracks and reminds me of the sacred and transcendent segments of my own hereditary cancer journey and that of our members.

The last Wednesday in September has been designated as Previvor Day, and this year it happens to fall on Yom Kippur. The convergence of the two led me to two message board posts from over a decade ago that currently reside in our Pearls of Wisdom forum, where older timeless posts live so that others can revisit them when needed.

The first pearl addresses Previvor Day. In the “I need a label” thread, our dear “Jordan,” who was a regular on our message boards back then, articulated what many in our community were feeling—that although they did not have cancer, they had experienced decisions, losses, and procedures that separated them from average-risk women, but they did not have a cancer diagnosis. Jordan posted:

“Ok, I have to admit. I need a label. Do we have one? You know, those that have the gene but have not had cancer. The ones going through all this research and deciding on proph surgeries, or not. We need more of a voice and a label, a name. I’ve never been one hung up on labels before but a lot has changed for me since this process begun. I feel if we had a label we could begin to have more of a voice. What are your thoughts? FORCE? Breast Cancer __________ (fill in the blank).” 

Jordan, and the group of high-risk women who shared her concerns, recognized that they were cancer stakeholders who shouldered a heavy burden: ongoing doctor appointments; frequent biopsies and screenings; fear; loss of relatives to cancer, and sometimes loss of breasts, ovaries, and fertility; and changes in body image, all due to the risk of cancer. Jordan also felt that uniting the segment of the community that didn’t have cancer could promote more awareness, prevention, and surveillance research, and begin to fill their huge unmet need for support and resources.

A sometimes serious and sometimes silly discussion of how to address this gap, both online and off, followed. The medical community at the time used the term “unaffected carrier” for someone who carries a mutation but isn’t affected by cancer. But in addition to sounding dismissive, that label didn’t include members of our community who were very high risk by virtue of a strong family history of cancer without a mutation, LCIS, or high exposure to radiation. Yet these people were living with the same concerns, fears, decisions, and need for support as others in our community. Eventually “previvor” (for “survivor of a predisposition to cancer”) was chosen as our label of choice, because we all felt that those living with high risk are survivors in their own right. Not everyone embraced the term initially (and many still don’t), but for that moment, previvor resonated with many and filled a need that would allow our community to unite and advocate on issues surrounding cancer risk, detection, and prevention. These issues were separate from resources and research focused on treatment but equally important.

“AmiH,” a member of FORCE’s board of directors and our volunteer webmaster, observed “that the word ‘survivor’ comes from the Latin root meaning ‘to live’.” That connection also resonated with many previvors who felt that the knowledge of their risk and the management options available to them increased their chance to live longer, healthier lives. Not everyone wants or likes a label, and we totally understand that. Some particularly dislike “previvor,” and we get that too. But being able to identify and validate an important group of high-risk stakeholders has led to a revolution resulting in much more awareness, resources, research, and support today than we ever had in the past.

The second pearl comes from a thread started by ‘SusanZ’ [Ziva] shortly after Jordan’s. “My guardian angel, a Yom Kippur lament” is one of the most heartwrenching articulations of previvorship. It captures the devastation and impact of HBOC on entire families. I hope you will read the entire thread, but here are some of the most poignant excerpts:

“Tonight is Yom Kippur. It is certainly a day to reflect on one’s own life. In the past, I have done that in a synagogue. This year I am doing that by my sister’s hospital bedside watching her die from breast cancer. I wanted desperately to ask her to be my guardian angel from heaven…I didn’t have the courage to ask this of her yet…the reality is that in her death she remains true to how she lived, she has continued to be my guardian angel by getting genetic testing. I have found out I am BRCA positive in time to protect myself. In her death she has saved my life, and the lives of many family members.”

 In a later post, Ziva writes,

“Tomorrow afternoon I have an appointment with my second PS [plastic surgeon]… and if there is no significant change in my sister’s status, I plan to walk across the hospital to his office and make that appointment. As Linda leaves this world I am going to fight to stay.”

“I am overwhelmed by your responses…Yesterday I did what I said I would. I kissed her good-bye…and marched across the hospital in defiance of this disease and met my 2nd PS [plastic surgeon].”

 and then this last heart-breaking post,

“My sister, Linda, died this evening at 6:30 as the Sukkot holiday rolled in. I closed my eyes and again asked my sister to forgive all my insults and past hurts that occur between people who love intensely, and be my guardian angel. Your support on this website has been so important to me. You are the ones who can really understand.”

Ziva and her family have remained involved with FORCE as passionate volunteers over the ensuing years, providing guidance, outreach, and support to others. Last night, 12 years after her initial post, Ziva revisited her thread and added these thought-provoking words:

“Well, it is 12 years now since I lost Linda, and all the above is still relevant and true for me. An update: I now have a beautiful and delightful 20-month old granddaughter named Maya Linda! I think she has my sister Linda’s smile and sometimes I feel Linda (and my mother) watching over us with love and grace. Maya Linda brings me the kind of joy I found so difficult to feel since my sister’s death. This is such a blessing. 

I believe there is something quite spiritual in sharing one’s stories with others who listen with respect and compassion and then listening to others willing to share their stories. In this way we can feel connected, significant, and develop courage. Thank you FORCE family for listening and sharing. Our connection gives me hope and courage.”

Ziva, thank you on behalf of all of us. As always your words have captured the essence of our community and of FORCE. This uniting of the community impacted by HBOC—those with cancer and those without—was the goal almost 14 years ago when I founded FORCE: to connect us through our shared experiences, and despite our differences to bring each of us courage, support, and hope for today and future generations.

Happy Previvor Day.

Be empowered and be well.

Sue

13 Developments That Have Helped the HBOC Community

September marks Ovarian Cancer Awareness Month. And September 23-30 we will celebrate National Hereditary Breast and Ovarian Cancer Week! Follow us on twitter, Facebook, and our website to see what we are doing to celebrate and to share your celebration ideas with us!

In honor of this time of year and in keeping with our “13 Things” theme, it seemed appropriate to share my list of 13 developments that have helped our community. Feel free to share your own additions to our list.

1) Discovery of BRCA1 and BRCA2 and advances in gene sequencing
Long before the discovery of the BRCA genes, scientists knew there was a link between breast and ovarian cancer. Geneticist Mary-Claire King first identified the existence of the so-called “breast cancer” genes. Scientists isolated the BRCA1 gene in 1994 and the BRCA2 gene in 1995, leading to the development of a blood test to screen for mutations in these genes. In the past, women with a strong family history of breast and/or ovarian cancer had no way to determine whether or not they had inherited the predisposition to cancer that ran in their family. With genetic counseling and BRCA testing, women can learn more about their risk for breast and ovarian cancers and make more informed health care decisions.Further progress in research and clinical genetics has allowed us to better quantify people’s risk for cancer. BRCA testing has improved and more mutations can be detected in these genes than previously.

Other genes have been identified that can also increase the risk for breast and ovarian cancers, although most increase the risk to a lesser degree than BRCA. Ambry Genetics and University of Washington are examples of laboratories offering genetic panels for people who have breast and ovarian cancers but have no known BRCA mutation in the family. Other tests are in development.

2) FORCE founded as a resource to educate, support, and unite the hereditary cancer community
In 1999, Facing Our Risk of Cancer Empowered (FORCE) was established as a devoted resource for the hereditary cancer community. Our founding principle was that no one should face hereditary cancer alone. Our mission has remained constant: to improve the lives of people and families affected by Hereditary Breast and Ovarian Cancer (HBOC) Syndrome. Our programs provide support, education, awareness, research, and advocacy. In the 14½ years since our inception, FORCE has provided compassionate support and evidence-based information to thousands of hereditary cancer survivors and previvors through our many programs.

3) Genetic Information Nondiscrimination Act (GINA)
Prior to 2008, widespread fear of genetic discrimination kept many people from taking advantage of genetic tests that could make a significant difference in their health care decisions and outcomes. This fear also prevented many people from becoming involved in medical research. The Genetic Information Nondiscrimination Act (GINA) became law in 2008. GINA prohibits health insurance and employment discrimination on the basis of genetic information or a genetic test result. FORCE and researchers from The Ohio State University recently published findings from a survey of consumer knowledge and attitudes about GINA. The study indicated that many people who undergo genetic testing are unaware of GINA.

4) Targeted cancer therapy
Targeted cancer therapies treat disease by interfering with molecules involved in tumor growth and progression (called molecular targets). By focusing on molecular and cellular changes found in cancer cells, targeted cancer therapies may be more effective than other types of treatment and cause fewer side effects. Because these therapies may benefit only a subset of cancer patients, they are usually accompanied by tests to determine whether a person’s cancer cells express the appropriate target.

One of the first molecular targets identified for cancer therapy was the estrogen receptor (ER) expressed in many breast cancer tumors. The FDA has approved several drugs for the treatment of ER-positive breast cancer, including tamoxifen, a selective estrogen receptor modulator, and aromatase inhibitors including anastrazole, letrozole, and exemestane.

PARP inhibitors block an enzyme used by cells to repair damaged DNA. Research is ongoing to determine if PARP inhibitors may work against cancers in people with BRCA mutations, since their tumor cells already have problems repairing DNA. The medications are being tested in clinical trials, and are not yet FDA-approved for use outside of clinical research.Learning more about the molecular defects of specific tumors should help to clarify the role of therapies targeting these defects. More research is needed to determine which targeted therapies work best for which tumors.

5) Oncotype DX, Mammaprint and other treatment decision tests
Not too many years ago, all women diagnosed with invasive breast cancer received the same chemotherapy. Although it effectively treats cancer, chemotherapy has serious side effects, and not all treatments are equally effective for all people. With the development of OncotypeDX, Mammaprint, and similar treatment decision tests, oncologists can use molecular techniques that examine the biology of the tumor, help predict which tumors have the highest likelihood of recurring and which patients would benefit most or least from chemotherapy.  With Oncotype DX, studies have shown that for patients with lymph node-negative, ER-positive breast cancer, a low recurrence score argues against the use of chemotherapy and a high recurrence score argues strongly in favor of the need for chemotherapy. Before these tests were available, doctors knew that not all patients benefit from chemotherapy, but they had difficulty determining which patients needed more aggressive treatment. Using these tests oncologists can help spare women whose chance of recurrence is very low from aggressive chemotherapy.

6) Discovery of fallopian tube origins of many hereditary gynecologic cancers
Gynecologic oncologists had long believed that most ovarian cancers start in the ovarian epithelium, the cells lining the surface of the ovary. However, emerging research suggests that many so-called “ovarian” cancers in BRCA mutation carriers begin in the fimbria (the area closest to the ovary) of the fallopian tubes (the passage that connects the ovaries to the uterus). Since this theory was first proposed, several studies have supported this observation. Recognition of fallopian tubes as the site of many BRCA-associated ovarian cancers has led pathologists to pay more attention to the fallopian tubes removed during prophylactic surgery; catching some “occult” or hidden cancers that would have been otherwise missed. This has also led to the discovery of Tubal Intraepithelial Carcinoma (TIC), precancerous changes in the tubes. Further research is continuing to determine if we can develop better detection and prevention methods, including whether removal of the fallopian tubes might lower the risk for gynecologic cancers in mutation carriers who are not ready to prophylactically remove their ovaries. Removing the fallopian tubes alone is not currently an approved risk-reduction strategy.

7) Serial sectioning of ovaries and fallopian tubes
As more doctors began recommending prophylactic bilateral salpingo- oophorectomy (BSO) to prevent ovarian cancer in high-risk women, pathologists began to discover small, unsuspected, “hidden” cancers had often developed in the ovaries and tubes of women by the time they had surgery. Although tiny, some of these cancers were still aggressive and further surgery or treatment was recommended. If not discovered and therefore left untreated, these cancers could recur later. Researchers at University of California at San Francisco published their findings on a pathology protocol designed to find these hidden cancers by looking at many ultra-thin cross sections of the removed tissue. Previously, pathology procedures called for examination of only a few representative samples. Since this extensive “serial sectioning” became standard-of-care protocol for high-risk women who undergo bilateral salpingo-oophorectomy (BSO), more women are being diagnosed at early stages of fallopian or ovarian cancer, before the disease has spread and while it’s still curable.

8) Laparoscopic and minimally invasive BSO
In the past, removal of the ovaries and tubes was always performed through a large abdominal incision that allowed the surgeon to view the organs being removed. The invention of the laparoscope–a tiny camera on the end of a surgical tool that can be inserted through a small abdominal incision—allowed gynecologic surgeons to achieve a similar outcome with a smaller incision, less pain, and quicker healing. Generally, women who have prophylactic laparoscopic BSO can go home the same day. Abdominal surgery requires several days of hospitalization.

Although on occasion laparoscopic procedures are converted to full abdominal surgeries if there is a complication or excessive bleeding, or if the surgeon needs to see more of the abdominal cavity, for the most part, minimally invasive laparoscopic surgery is standard-of-care for prophylactic BSO. The development of robotic equipment has further improved a surgeon’s visibility of and access to abdominal organs, especially during more complicated surgeries to remove large or invasive tumors.In some cases gynecologic surgeons recommend hysterectomy (removal of the uterus) as well as BSO. This additional surgery can often be performed vaginally through another small incision at the time of the BSO.

9) Screening breast MRI
Women with BRCA mutations have a lifetime breast cancer risk as high as 85%. Their risk begins at a younger age than for sporadic breast cancer, when breast tissue is very dense and harder to image by mammography. In the past decade, researchers began studying whether magnetic resonance imaging (MRI) could be a more sensitive screening tool for breast cancer in high-risk women. Since 2004 several papers have consistently reported that breast MRI screenings of women with BRCA mutations find more early-stage cancers. Earlier detection increases the chance of successful treatment and long-term survival: this has also been shown in these studies. Annual MRI in now standard-of-care for breast cancer screening in women who are high-risk due to a mutation or a strong family history of cancer.

10) Mastectomy advances
Radical mastectomies were performed as standard treatment up until the 1970s. This disfiguring surgery removed all of the breast tissue, lymph nodes under the arm on the affected side, the muscle underneath the breast, and the nipple and areola, leaving only enough skin to close the incision. Lymphedema and long-term pain were common after radical mastectomies. Over the years, this procedure was replaced by less extensive and less invasive surgeries that do not compromise survival. Development of modified radical mastectomies, skin-sparing mastectomies, and nipple-sparing mastectomies has led to fewer complications, fewer long-term side effects, more aesthetic outcomes, and in some cases, retention of some sensation in the breast.

11) Sentinel lymph node biopsy
Sampling underarm lymph nodes of breast cancer patients allows doctors to determine if invasive disease has spread beyond the breast, and affects prognosis and treatment recommendations. Prior to sentinel node biopsies, women who were diagnosed with breast cancer faced axillary dissection—removal of multiple lymph nodes—to stage their cancer. Axillary dissection, however, increases the risk for lymphedema, painful and dangerous swelling of the arm. Sentinel lymph node biopsy (SLNB) allows surgeons to sample only one or a few lymph nodes that are most likely to contain any cancers cells that have spread beyond the breast. If the “sentinel” lymph node or nodes are free of cancer, most patients do not have additional nodes removed. Removal of fewer lymph nodes lowers the risk for lymphedema and improves quality of life in breast cancer survivors. A large study of 5,600 women published in 2010 confirmed the value of SLNB. It showed no difference in disease-free- or overall-survival between women who had negative sentinel nodes and received full axillary dissection compared to those who received sentinel biopsy alone.

12) Reconstruction advances
Reconstruction has evolved over the years, delivering more options for rebuilding natural-looking breasts after mastectomy with less extensive surgery. Doctors can move fat from the belly, thighs, or hips to reconstruct breasts. In the past, these tissue transfers required extensive loss of muscle. With the development of perforator flaps, the same outcomes are achieved while sparing muscles. Fat transfer can augment or rebuild breasts using liposuction and fat injection procedures.New silicone implants are softer and are believed to last longer than older implants. They may also be less likely to rupture, leak, and deflate. A new type of expander being studied allows women to control their own expansion process. Direct-to-implant surgery offers patients the opportunity to forgo expansion, reducing the overall reconstruction timeline with less discomfort.

13) Survival data on prophylactic oophorectomy
Women with BRCA mutations have a lifetime risk for ovarian cancer that is many times higher than women in the general population. Since the discovery of the BRCA genes, many research studies have documented the effectiveness of prophylactic mastectomy and oophorectomy for lowering risk in high-risk women. But until 2010 there was little published research to show that these surgeries improved survival for women with BRCA mutations. In 2010, researchers from the University of Pennsylvania published their research on behalf of a large international collaboration, following over 2000 women with BRCA mutations of whom about half chose to undergo one or more risk-reducing surgeries. The compelling results showed that risk-reducing surgeries significantly reduced cancer diagnoses, and that risk-reducing removal of ovaries lowered cancer-related and overall deaths.

Applying Personalized Medicine to Disease Screening and Prevention

Personalized medicine uses information about an individual’s genetic make-up to deliver the right screening, prevention, or treatment options at the right time to achieve the best medical outcome. Genetic counseling, risk assessment, and genetic testing to determine inherited predisposition for diseases are important and growing areas of personalized medicine that further this goal.

Critics have raised concerns that identifying and treating people who are at risk for disease necessarily leads to “over-medicalization” of health care and increases cost and the possibility of causing harm. Evaluating the risks and costs versus benefits of disease prevention and control, however, is complex and depends on the disease in question, available screening and risk-management options, individuals or populations who are most at risk, and their level of risk for the disease. Given our limited resources and focus on containing health care costs, we will move beyond a one-size-fits-all approach to health only when we are willing to carefully consider each of these variables, rather than discounting all risk assessment, screening and prevention as over-treatment.

Not all risk is the same
Risk changes over the course of a lifetime, depending on genetics, lifestyle and other factors. Preventive care and screening recommendations for people of average risk are based on studies of thousands of people in the general population—sometimes they are not adequate for people who have a higher risk for a particular disease. Personalized medicine allows us to identify people with higher-than-average risk and provide interventions that can improve their health outcomes. For example, the American Cancer Society recommends annual mammograms beginning at age 40 for women with an average risk for breast cancer. But women with BRCA mutations, who face a higher lifetime risk for breast cancer at a younger age, and tumors that may develop faster and more aggressively, need more frequent and rigorous screening that begins at an earlier age and involves annual MRI surveillance.

Not all diseases are the same
Diseases develop and behave differently and have different impact, morbidity, and mortality, which must be considered when weighing the cost and risks compared to the value of screening and prevention. Impact of a disease includes the number of people affected and the consequences of diagnosis and treatment on survival and quality of life. Basal cell skin cancer and ovarian cancer illustrate these differences.

Roughly 2.8 million people in the United States are diagnosed with basal cell skin cancer yearly, compared to about 22,000 ovarian cancer diagnoses. Basal cell cancers can be detected through skin exams, and almost all cases are cured. With no reliable detection or screening, ovarian cancer is most often found late, when the five-year cure rate is less than 50%. Ovarian cancer patients require extensive surgery, chemotherapy, and sometimes radiation, often with profound negative effects on quality-of-life. Although more people are affected by basal cell cancer, more people die of ovarian cancer. Screening and prevention recommendations for a common, detectable, and treatable disease like basal cell cancer require different considerations than those for a less common cancer (like ovarian cancer) that cannot be detected early, carries a poor prognosis, and is accompanied by aggressive treatment. It makes sense to focus efforts and apply technology to identify those in the highest risk category for deadly diseases such as ovarian cancer and prevent them whenever possible.

Not all interventions have the same risks or benefits for everyone
We can predict risk for some diseases like Huntington’s, for which we have no effective or proven intervention. However, many diseases, such as breast cancer, have interventions that lower the risk for or improve the odds of detecting the disease at it’s earliest and most treatable stage. Each disease intervention option has unique risks, costs, and benefits that should be considered individually.

MRI is a sensitive tool that can detect breast cancers that are too small for a mammogram to find. But MRI screenings are expensive, and they often find suspicious but harmless breast changes, requiring a biopsy to assure that they are benign. For these reasons, experts don’t recommend screening breast MRI for women of average risk for breast cancer. Women at high risk have a greater likelihood of an abnormality being actual cancer, and that often tips the scales in favor of increased surveillance, even if that means a greater chance of needing a biopsy. Long-term research on high-risk women shows that MRI detects breast cancers at an earlier stage resulting in less extensive treatment.

Having a BRCA mutation raises the lifetime risk for ovarian cancer up to 50%, compared to 1.5% for women with average risk. Prophylactic bilateral salpingo-oophorectomy (removal of the ovaries and tubes) is the most effective way to reduce ovarian cancer risk, but like all surgery, the procedure has its own potential for risk and harms: complications from anesthesia, infection, and early menopause, which can be associated with long-term health and quality-of-life consequences. Surgery is also costly. On the other hand, research has shown that BSO improves survival in high-risk women. Given the costs, risks, and benefits of prophylactic surgery versus the consequences of an ovarian cancer diagnosis, this intervention offers more value to women at very high risk and less value to average risk women.

Research shows that prostate cancer screening using PSA increases detection of this cancer but may not improve survival for many men. PSA screening has risks and limitations including: many of the cancers found are not symptomatic and will not affect life-span or quality-of-life; PSA tests can yield many false-positive results leading to unnecessary biopsies; treatment of prostate cancer can lead to side effects in many patients. Given this, the United States Preventive Services Task Force (USPSTF) issued guidelines that recommended against PSA screening for men of average risk. However, recent research suggests that men with BRCA 2 mutations face a higher lifetime risk for more aggressive, younger-onset, prostate cancer than men in the general population. Applying personalized medicine to their guidelines, the USPSTF qualified that “This recommendation…does not consider PSA-based testing in men with known BRCA gene mutations who may be at increased risk for prostate cancer.” 

Not all information is clinically useful
Before BRCA mutations were identified, individuals with a strong family history of cancer had no way to know whether they had inherited a very high risk for cancer. Basing their risk on family history alone, these women sometimes pursued prophylactic surgery, even though their lifetime risk was no higher than the average woman’s. The availability of BRCA testing improves decision-making for high-risk women, giving them the opportunity to learn more about their personal risk and make evidence-based health care decisions.

The same advances that make BRCA genetic testing possible have also led to the development of other tests that may not be as useful. Genetic testing allows researchers to understand how diseases develop and design better options for screening, prevention and treatment. But not all genetic tests should be offered to the general public for decision-making purposes; particularly those that do not provide “actionable” information that people can use to improve their health or quality of life.

Informed decision-making
Given credible information, people are capable of weighing the costs, harms, and benefits of different medical interventions. Genetics experts can help to guide people through the maze of factors described in this blog to make personal informed decisions about their care.

BRCA is just the tip-of-the-personalized medicine iceberg. Genetic tests have been developed that can look at tumor cells to determine the best treatment or predict the likelihood of people having side-effects from a particular therapy.  Granted, personalized medicine is not an exact science, and we are not yet able to apply it to all people and all diseases. But it makes sense to use evidence-based interventions to save and improve the quality of as many lives as we can. As a society, we need to continue to invest in the research, translation, and application of personalized medicine, risk assessment, and genetic testing to determine the best candidates for the best interventions at the best time.