HBOC Week 2012: A Call to Arms

As we begin HBOC Week and approach Previvor Day 2012, I am again reminded of how far we have come and how far we still have to go in the fight against hereditary cancer.  The growth of our organization, message boards, mailing lists, and Facebook and Twitter pages tells the story: more people than ever are aware of hereditary cancer risk and are turning to FORCE for information, support, and resources. This is all good news, but at a recent meeting at the Centers for Disease Control (CDC), the Director of the Office of Public Health Genomics, Dr. Muin Khoury, emphasized that most people who are at inherited high risk for cancer are unaware of their status. Recognizing that identification of people with BRCA and Lynch Syndrome mutations and offering medical intervention on their behalf can save lives, the CDC is now working on an initiative to integrate genomic education and awareness into the states’ Departments of Health.

These programs are sorely needed. On a daily basis through our programs we hear from people who are unaware of their high cancer risk or their options to manage it. The tales we hear illustrate how much work is yet to be done. We hear of high-risk women who are denied breast cancer screening and told that they are too young to have mammograms or that they do not need MRIs, survivors who are not aware of their high risk for future cancers, and people who meet expert guidelines for genetics evaluation but are not referred for genetic counseling. Media reports on screening guidelines often omit the fact that recommendations for people of average risk are not adequate for those who fall in the high-risk range. Some vocal individuals and groups malign genetic evaluation and risk management as unimportant or overtreatment. And stories like the one recently published on BloombergBusinessweek.com show how patients pay the price when health care providers who lack training in genetics misinterpret test results.

But despite these setbacks we have had a lot of wins. Earlier this year a generous gift from Mindy and Jon Gray created the Basser Research Center for BRCA1 and BRCA2 at the University of Pennsylvania. It is the first comprehensive center dedicated solely to the pursuit of research and provision of care relevant to BRCA1 and BRCA2. The United States Preventive Services Task Force incorporated information about BRCA into their recommendations for ovarian and prostate cancer screening. The CDC’s Actions to Save Lives Now, a workshop on incorporating genomics into public health, focused on bringing the public lifesaving education and awareness, and that’s a great step forward. In a few weeks we will host our 7^th annual Joining FORCEs Against Hereditary Cancer Conference with record-breaking attendance and participation.

HBOC Week/Previvor Day logo

As today marks the start of the third National HBOC Awareness Week and next Wednesday is Previvor Day, our goal is to attract more attention than ever. Let’s focus on the positive, and use this opportunity to save lives through education. 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 eduation, support, and resources they need to make informed decisions about their risk.

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.

13 Things That Jewish People Should Know About Hereditary Breast and Ovarian Cancer

Before I was diagnosed with breast cancer at age 33, cancer was not on my radar. Despite the fact that my paternal grandmother had died young of so-called “abdominal cancer,” none of my health care providers indicated that I might be at high risk for cancer. My health care team treated my diagnosis of young-onset breast cancer like a lightning bolt out of the sky. It wasn’t until after my initial treatment (a unilateral mastectomy) that I read a magazine article and learned of several significant red flags for an inherited BRCA mutation. After reading the article I became concerned that my cancer might be hereditary. The article talked about the link between young-onset breast cancer (like mine!) and ovarian cancer (which my grandmother likely had) and BRCA mutations. It also mentioned the relevance of a family’s health history on the paternal side (in my case the only cancer in my family was on my father’s side). No doctor had ever expressed interest in the cancer on my father’s side of the family. Perhaps the detail that was most surprising to me was the high prevalence of BRCA mutations in people of Easter European Jewish descent. All of the factors mentioned in the article which raised the suspicion of a mutation applied to my situation. Had I known this information before my mastectomy, I would have pursued genetic counseling and testing and made different surgical decisions at the time of my diagnosis.

Even now, 16 years after my diagnosis, as I give presentations on hereditary cancer, I still frequently meet Jewish people who have no idea of the high prevalence of BRCA mutations in this community. Most Jewish people are aware of the dangers of Tay-Sachs disease, another genetic disorder which is also prevalent in Jewish populations. Yet there are still many people who are Jewish and have a family history of cancer who have never heard of BRCA mutations and are unaware of the availability of genetic counseling and testing. Learning about BRCA   almost a year after my initial diagnosis of breast cancer was eye-opening. I learned the importance of people doing their own researching and advocating when it comes to health care decisions.

In keeping with our “13 Things” theme during 2012, I present my list of what Jewish people should know about hereditary breast and ovarian cancer, with the hope that this list will be spread far and wide beyond the FORCE community in order to save lives.

1. BRCA mutations have been found in people of every ethnicity. But people of Eastern European Jewish ancestry have the highest known incidence of BRCA mutations, and hereditary breast and ovarian cancer.
2. About 1 in 40 people of Jewish decent have a BRCA mutation, about 10-fold higher than other populations.
3. Women with a BRCA mutation have up to an 85% lifetime risk for breast cancer and a 50% lifetime risk for ovarian cancer.
4. About 40% of Jewish women with ovarian/fallopian tube cancer and 20% who have premenopausal breast cancer have a BRCA mutation.
5. BRCA mutations are associated with increased risk for several types of cancer, including breast (both male and female), ovarian, fallopian tube, primary peritoneal, pancreatic, melanoma, and prostate .
6. Each child of an affected parent has a 50% chance of inheriting a BRCA mutation.
7. BRCA mutations can be passed down equally from fathers or mothers to sons or daughters.
8. Beginning at age 40, men with BRCA mutations should discuss with their doctor the benefits, limitations and risks of prostate screening. Preliminary research suggests that prostate cancer in men with a BRCA mutation may be more aggressive than prostate cancer in men who do not have a BRCA mutation. Men with BRCA mutations are at risk for melanoma, male breast and pancreatic cancer as well.
9. People who test positive for a BRCA mutation have options to lower their risk for cancer or detect it at an earlier, more treatable stage.
10. The majority of BRCA mutations in Jewish people occur in one of three genetic sites. Genetic testing usually begins with a Multisite 3 panel that looks for these common mutations and is less expensive than full BRCA testing.
11. In couples where both individuals have a BRCA2 mutation, it is possible for children to inherit a rare and deadly disease known as Fanconi Anemia, which is more common in people of Jewish descent. Couples concerned about this possibility should consult with a genetics expert.
12. Genetic testing for BRCA is performed from a blood sample or cheek swab.  The test itself is simple, but it is not always straightforward. Consulting with a genetic counselor is the best way to assure the correct test is ordered, results are properly interpreted and an appropriate course of action is discussed.
13. The majority of people who have a BRCA mutation or a family history of cancer are unaware of their increased risk for hereditary cancer.  Awareness is critical to saving lives.

Visit our website for more information about genetic counseling and testing. Visit our FORCE in the Jewish Community page to watch our video and learn about ways you can help raise awareness about BRCA in Jewish people.

13 Facts that Men with Hereditary Cancer Risk Should Know

As we approach Father’s Day we would like to call attention to an often forgotten group: men who have a BRCA mutation or a family history of hereditary cancer. Although men don’t get ovarian cancer and their risk for breast cancer is very low, we are learning more and more about how hereditary cancer risk affects them.

FORCE responded to the United States Preventive Services Task Force’s (USPSTF) preliminary guidelines that recommended against prostate cancer screening for all men. Based on emerging research, we encouraged the panel to revise the text to state that the guidelines did not apply to men with BRCA mutations. The USPSTF incorporated our suggestion into its final guidelines. Accomplishments like these remind us how important FORCE’s advocacy work is. Men with BRCA mutations are important cancer stakeholders. Our goal is to assure that they have a voice advocating for their concerns when government cancer policies are developed.

In keeping with our 13 Things theme and in honor of high-risk men, here are 13 facts men need to know about hereditary breast and ovarian cancer.

1. Men with BRCA mutations have increased risk for breast and prostate cancer, and like women with mutations, their risk for pancreatic cancer and melanoma is also elevated. Men with BRCA2 mutations have greater risk than men with BRCA1 mutations.
2. Although men with BRCA mutations have a greater cancer risk than men in the general population, their risk for cancer is lower than most women with a mutation.
3. Because preliminary research suggests that hereditary prostate cancer tends to be a more aggressive form of the disease, the USPSTF advises that screening guidelines developed for men in the general population should not be applied to men with mutations.
4. BRCA mutations have been found in people of every ethnicity, but not with the same frequency. About 1 in every 300 to 500 people carry a BRCA mutation. About 1 in 40 people of Ashkenazi Jewish descent have a mutation.
5. Breast screening recommendations for men with a mutation include regular breast self exams and twice yearly clinical exams by a medical professional beginning at age 35. A baseline mammogram is recommended at age 40 and annual mammograms thereafter are advised, depending on the baseline results.
6. Men with mutations or hereditary cancer in the family should discuss with their doctor the benefits, limitations, and risks of prostate screening using PSA and digital-rectal exam beginning at age 40.
7. The international IMPACT study is looking at the benefit of PSA screening in men with and without BRCA mutations. Full results from this research will be available in 2020.
8. BRCA mutations can be passed down equally from either parent to sons or daughters.
9. When both parents have a BRCA2 mutation, their children may inherit a rare and deadly disease known as Fanconi Anemia. This is more common in people of Jewish descent. Couples concerned about this possibility should consult with a genetics expert.
10. Couples who are concerned about passing a mutation to their children may want to speak with a fertility expert about in vitro fertilization and preimplantation genetic diagnosis that screens embryos for BRCA mutations.
11. Early research on PARP inhibitors for treatment of prostate cancer has been promising. Currently, some open PARP inhibitor studies are enrolling men with advanced prostate cancer.
12. Coverage for BRCA testing in men can vary depending on their insurance plan. A genetic counselor can help men determine if their insurance will cover testing.
13. Men who are concerned that the cancer in their family may be hereditary should consult with a genetics expert before pursuing genetic testing. FORCE can provide information on locating genetics specialists. Genetics consultations are typically covered by insurance.

If you are a man with a BRCA mutation or hereditary cancer in your family, please complete our survey for high-risk men, read about our advocacy efforts on behalf of the men in our community, visit our expert-reviewed information section for men, and join our mailing list to stay updated on new information, research, and programs specific to men with BRCA mutations. Please consider participating in this telephone focus group research study for high risk men.

FORCE helped unite and organize the female hereditary cancer previvor and survivor populations to advocate for more resources; we need to do the same for the men in our community. If you have high-risk men in your life, please let them know about these resources. Please help us raise awareness, spread the word, and save lives by sharing this blog, and printing and sharing our “13 Things Men Need to Know” flier.

Advocating for Men: Responding to the USPSTF Recommendations against PSA

I am concerned both on a professional and personal level about the United States Preventive Services Task Force (USPSTF) recent draft guidelines that recommend against PSA screening for men of average risk or who are high risk by virtue of a family history of cancer. FORCE has prepared a position statement in response to this draft and we are encouraging our members to read our statement and submit commentary to the USPSTF.

My father died of prostate cancer. No matter how much I told him about BRCA, the hereditary cancer link, and his own risk for cancer, he ignored his health and refused to get checked. When he developed a severe case of pneumonia that put him in the hospital, he had his first physical exam and blood work in 35 years. His PSA was elevated. Only after he had serious symptoms did he finally agree to a biopsy; by then the prostate cancer was advanced. It took his life the following year. I have two brothers and worry about them. Like most parents with a BRCA mutation, I also worry about whether or not I passed my mutation on to my son.

Although it is true that men with mutations do not have the same extraordinary high risk as women with mutations, men do have a very elevated lifetime risk, as high as 33%. Like other cancers in mutation carriers, BRCA-associated prostate cancers are different than sporadic prostate cancers. In men without mutations, prostate cancers are often slow in onset, asymptomatic, and may never progress or affect quality-of-life or lifespan. Recent research, however, shows that men with BRCA2 mutations who develop prostate cancer are more likely to develop cancer at a younger age, have an aggressive form, and die of the disease compared to those in the general population. So guidelines for prostate cancer screening for the general population may not apply to those with mutations. The ongoing IMPACT study, an international collaboration, is looking at whether PSA can improve detection of prostate cancer and survival in mutation carriers.

In drafting their latest recommendations, the United States Preventive Services Task Force (USPSTF) did not take into account any of the published studies that relate specifically to men with mutations. FORCE plans to submit our position statement to the USPSTF, strongly urging that the guidelines be revised to clarify that they are not meant for men who have a BRCA mutation or a high likelihood of carrying a mutation. Please read our full position statement on the guidelines. The USPSTF  is accepting public comments on the proposed guidelines until November 10. We have a chance to influence the final recommendation so that it takes into account high-risk men with mutations. Let’s advocate for the men in our community and help save lives!

If you are a man with a BRCA mutation and you are interested in participating, visit the IMPACT study website.