Talk

Guest post from Lisa Kessler, DNA Direct’s Senior Genetic Counselor:

A recent article in the New York Times about red flags for hereditary cancer went into detail about specific findings in families. About 5-10% of cancers are thought to be strongly hereditary; for people who worry about their genetic risk, and who have a family history consistent with a hereditary cancer syndrome, genetic counseling and genetic testing can be extremely useful for decisions about personal and family health.

The article emphasizes the need for “intensive professional counseling” for individuals and families concerned about hereditary cancer risk, and I agree completely. I believe that genetic counseling helps people understand whether testing is medically indicated—and why, learn the benefits and limitations of testing, and understand why a certain family member might be the most informative person to test.

At DNA Direct, genetic counseling is required for people considering testing, both before and after hereditary cancer testing. Our counseling model provides people with an opportunity to learn about the testing to determine if it’s right for them — and for their families.

Most people aren’t familiar with the type of information discussed in a genetic counseling session. At DNA Direct, a pre-test genetic counseling session for someone considering BRCA1 and BRCA2 testing (genes for hereditary breast and ovarian cancer risk) includes, but is not limited to:

• discussion of personal medical history related to cancer
• drawing and interpretation of a 3-generation family health history diagram
• discussion of who in the family is the most appropriate member to test first
• background information about genes, chromosomes, and inheritance
• specific cancer risks associated with having a BRCA1/2 mutation
• options for cancer screening and prevention for people at high risk
• discussion of the benefits and limitations of BRCA testing, including psychological impact
• understanding the possible results of testing

If people proceed with testing through DNA Direct, a board-certified genetic counselor discloses the test results over the telephone. Then, clients can access a detailed, 5-chapter Personalized Report that reviews much of the information discussed during the pre- and post-test consultations. Because people often have questions after receiving their results, our genetic counselors are available to answer questions or simply for support, for all who test with us.

Not all patients can see a genetic counselor in person. Providing counseling by telephone gives us at DNA Direct the chance to increase access to genetic services in a responsible way, with a focus on ensuring reliable, easy-to-understand and informative results.

Lisa Kessler, MS, CGC
Senior Genetic Counselor

Amy Harmon looks at the issue of privacy, fear of discrimination, and the very real repercussions some people are facing as a result of the tension between important medical information and lack of comprehensive legislation to protect patients’ genetic privacy.

She quotes Francis Collins, director of the National Human Genome Research Institute at the NIH, “It’s pretty clear that the public is afraid of taking advantage of genetic testing. If that continues, the future of medicine that we would all like to see happen stands the chance of being dead on arrival.”

I don’t think it’s as dire as that, but all of us — patients, physicians, industry and thought leaders — need to push for systemic solutions. Genetic testing is redefining the practice of medicine, and our convoluted infrastructure of delivering healthcare needs to adjust to accommodate it.

Harmon’s profiles of people who have chosen to test, not to test, and to test anonymously by paying for testing themselves illustrate how this tension has a fundamental impact on peoples’ health and families’ lives: (more…)

Stalking Strangers’ DNA to Fill in the Family Tree: How far would you go to find out about distant relatives and common ancestry with strangers? Many of the situations described here seem a little, shall we say, outside the bounds of propriety and into the realm of CSI. Have we all been watching too much crime TV?

ACS Recommends Regular Breast MRIs for Women at High-Risk for Breast Cancer: Listen to Elizabeth Morris from Memorial Sloan Kettering discuss the new guidelines on NPR’s “Science Friday with Ira Flato“. Women should consider annual MRIs if they’ve got a strong family history, if they’re a BRCA mutation carrier, if they’ve had chest radiation treatments for conditions such as Hodgkin’s Disease. As a caller on this program points out, recommendations are inevitably two steps ahead of the medical establishment and insurance coverage. If you’re interested in pursuing MRIs, head to the big cities and major medical centers for radiologists who can perform and accurately read these MRIs. Now, to call my doc for a referral for an MRI…. (Update: Check out Emily DeVoto’s Antidote for counterspin on these recs.)

Chimeras: A New Kind of Twin: For the first time, researchers have identified twins that are identical on their mother’s side (same egg), but share only half of their father’s DNA (different sperm). Dr. Vivienne Souter, lead investigator in the journal article reporting this finding, says that while the term semi-identical provides some idea of how the twinning occurred, it is “an oversimplification.” I’ll bet! But I can’t wait to hear more.

Technorati Tags: ancestry, nonpaternal events, dna testing, family tree, genealogy, medical guidelines, american cancer society, breast cancer, MRIs, screening, high risk, genetic chimera, twins, genetics, intersex, hermaphrodite

Last night, our local PBS affiliate aired a segment on “Genetic Testing Through the Web“. (You can view the full segment online here.) Ironically, they spent more time discussing traditional methods of genetic counseling and testing services, as provided by UCSF’s Cancer Risk Program. But, they did a great job explaining what genetic counselors do and why genetic counseling is a critical component of genetic testing. It’s always good to to see GCs getting their props.

As with just about every piece that spotlights genetic testing, they profiled genetic testing for hereditary cancer risk. If it isn’t cancer, then it’s Huntington’s Disease. How come we never hear about carrier screening, and other types of genetic testing that are relevant to a much larger population?

With media coverage, I’m always fascinated to see the story-angle they take and how the final edit plays out. (more…)

In the December 6th issue of Journal of the National Cancer Institute, researchers report that BRCA1 and BRCA2 mutations are more common than has been generally thought, and they seem to be associated with a greater risk for a number of cancers.

However, as lead investigator Dr. Harvey A. Risch told Reuters Health,

“For breast and ovarian cancer and perhaps other cancers as well, the lifetime risks for carriers of BRCA1 and BRCA2 mutations are not uniform — they depend on exactly which mutation is carried. Some mutations have higher risks and some have lower risks.”

The risk of cancer also appears to be related to the position of the mutation on the gene.

Abstract: Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin-Cohort Study in Ontario, Canada. Journal of the National Cancer Institute, Vol 98(23), 6 December 2006, pp. 1694-1706(13).

Technorati Tags: cancer, cancer risk, risk factor, brca1, brca2, genes, genetic risk, research news

Since DNA Direct first began offering CYP2D6 testing for tamoxifen efficacy last month, we’ve had calls from women asking, “how come my doctor didn’t recommend this?” and “why doesn’t my doctor know about this?”

Dr. Kevin Knopf, a respected medical oncologist who specializes in breast cancer, has an explanation in his post this week “Something to Worry About? Tamoxifen Effectiveness.” He wrote this post upon first learning about tamoxifen and 2D6 — from his newspaper. He says:

It is also interesting how oncologists and other doctors find out about news this big – were it not for my newspaper I don’t know when it would first come to my attention (I’ll let you know next month!) When I asked my partner if he had heard about it, it was news to him. There are often no “mass broadcasts” of “breaking news” –e.g. nothing on my email yet. So this can create anxiety for patients who might see something before their oncologist does. I think the best approach would be to let the information get absorbed prior to making any decisions about tamoxifen and to seek guidance from your personal oncologist.

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The only recent coverage I’ve seen so far about the FDA’s relabeling of tamoxifen on is from the PGx Reporter, which is subscription-only. Here’s their public excerpt:

FDA Panel Leans Toward Including CYP2D6
Dx in Tamoxifen Label, But is Split on Language

The Pharmaceutical Science Clinical Pharmacology Subcommittee was split over whether the label should “recommend” the genetic test or make it an “option” for health care providers and patients to discuss.

As it considers just how strong the wording on the label should be, the FDA is looking at the role of endoxifen (the active metabolite), 2D6, and drug interactions.

We’re getting many inquiries ourselves into the Tamoxifen 2D6 Test. Here are recently asked questions and answers, and previous posts on Tamoxifen and 2D6 Testing.

Technorati Tags: tamoxifen, cyp2d6, genes, drug metabolism, fda recommendation, drug interactions, genetic test, dna

If you or someone you love is considering genetic testing for breast cancer, you must read Aliyah Baruchin’s article, “In Breast Cancer, There Is a Single Agenda: Stay Alive” from last week’s NY Times. She eloquently writes about her experience, illustrating the complexity women face when considering the BRCA test.

“I was petulant about BRCA testing from the moment it was first mentioned to me,” she begins.

After I had a mastectomy, though, the idea of more surgery became unmanageable. Losing a breast was extraordinarily difficult. The body wants its own coherence; it objects, in the most strenuous terms possible, to any structural loss. No more parts for sale to the lowest bidder, was all I could think afterward. Everything else I have, I want to keep.

But here’s the important thing, the thing I learned that changed me for good: in practical terms it was all bluster. I was 43, a working journalist, with a 3-year-old daughter and a remarkable husband. Of course I was going to be tested.

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Ryan (the CEO and founder of DNA Direct) and I just returned from an FDA meeting where members of the Clinical Pharmacology Subcommittee, a group composed of doctors and researchers, made an important decision about the breast cancer drug tamoxifen. As Lisa Lee described last week, the purpose of this meeting was to decide whether to recommend changing the tamoxifen package insert, also known as the drug label, to include information about how the 2D6 gene is a predictor of response to tamoxifen.

Clearly the decision of the Subcommittee is a historic moment, both for the emerging field of pharmacogenetics (or how genes influence a patient’s response to drugs) and, most importantly, for the breast cancer community. After all, hundreds of thousands of women are on the drug tamoxifen, and more women are put on the drug every day. The fact that some of them may not be receiving full benefit from tamoxifen because of their genes — therefore increasing their risk of cancer recurrence — could not be more important for breast cancer patients to know about.

So, what did the Subcommittee recommend? (more…)

Speaking of breast cancer - we’re on a roll this month! - there are very important happenings at the FDA next week. On October 18, the FDA will to evaluate recent research regarding 2D6 gene variants and response to the breast cancer drug, tamoxifen, and whether this research warrants any warnings or changes to the tamoxifen package insert.

Here’s a link to the FDA’s Executive Summary on Tamoxifen and 2D6. (Clicking this link will download a .PDF.)

In concert with the hearing, DNA Direct is launching our first drug metabolism test: 2D6 testing with personalized test results interpretation for tamoxifen. (Testing can be ordered online at the Genes&Drugs website.) Below is DNA Direct’s backgrounder, which explains the test, the research and why we’re offering 2D6 Tamoxifen testing to certain patient populations.

TAMOXIFEN & 2D6 BACKGROUNDER

Recent research on tamoxifen has shown that potentially up to 7-10% of women with breast cancer may not receive the full medical benefit from taking tamoxifen, because of their unique genetic make-up. These women have a special version of a gene (CYP2D6, commonly referred to as 2D6), which may reduce the effectiveness of tamoxifen and increase their chance of breast cancer recurrence. With over 500,000 women currently taking tamoxifen, this research has wide-reaching implications. (more…)

I’ve been looking for something other than breast cancer to talk about since I just posted on hereditary breast and ovarian cancer, because September was Ovarian Cancer Awareness Month…but I can’t avoid it. Everyone’s wearing pink ribbons and news about breast cancer abounds:

• A new breast cancer gene has been found: BRIP1.
• The White House issued an official proclamation by the President that October is National Breast Cancer Awareness Month.
• The FDA is meeting next week to discuss tamoxifen, a drug metabolism gene called CYP2D6, and their relationship in terms of risk for breast cancer recurrence.

Stay tuned for more info on the FDA hearing next week….

Technorati Tags: breast cancer, hereditary cancer, genes, brip1, tamoxifen, drug metabolism, breast cancer recurrence

Yesterday in San Francisco, thousands of people turned out for the Race for the Cure, a fundraising event put on by the Susan G. Koman Foundation for breast cancer awareness. Every year with few exceptions I have raced in honor of my mother, who was first diagnosed with breast cancer at age 35. She is a testament to what it means to be a survivor, zealously pursuing a life defined not by so many surgeries and recoveries but by her love for family, friends and personal interests. My mother has never considered herself a patient or a victim. She is, as my grandmother once put it, “a fireball that descended on Phoenix in 1960 and has been lighting things up ever since!”

As you know from the previous post, it’s also ovarian cancer awareness month. What does breast cancer have to do with ovarian cancer? A small percentage of people have hereditary forms of these cancers, which are caused by inherited changes in the BRCA1 or BRCA2 gene. These gene changes put you at increased risk for both ovarian and breast cancer.

Genetic testing is available, but it’s not for everyone — and it should be done in concert with genetic counseling.

Read more:

• How Breast & Ovarian Cancers Are Inherited
• The BRCA Genes and What They Do
• Considering Genetic Testing for Breast & Ovarian Cancer
• FORCE: Facing Our Risk of Cancer Empowered. FORCE is a nonprofit organization for women with increased risk of cancer due to family history and genetic status, and for members of families in which a BRCA mutation may be present.
• Genetic testing services at DNA Direct

Technorati Tags: breast cancer, ovarian cancer, hereditary cancer, inherited cancer, BRCA1, BRCA2, genetic testing, race for the cure, susan g koman foundation

Ovarian cancer awareness month has begun with good news at the intersection of cancer and genetic research. In the August issue of Oncogene, one of the world’s leading cancer research journals, Canadian researchers published a new model to identify ovarian cancer genes. This marks a big step toward improving treatment for the disease.

In a news release, Dr. Patricia Tonin, a cancer geneticist at McGill University Health Center in Montreal, says:

Our findings now provide tangible targets for effective drug development. Up to now, there has been little in the way of treatment options for this disease, which is one of the most lethal of cancers.

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New, Promising Treatments for Cystic Fibrosis. Forbes has a long article on two drugs, Inspire and Vertex, that are in late stage clinical trials. The article has a great explanation of how cystic fibrosis on a cellular level causes its symptoms - breathing, lung, and digestive problems. (Forbes online is free, but they require registration)

Affymetrix to Launch a 1 Million-SNP Microarray. The new GeneChip will debut early next year, at around $500. Affy is also dropping the price of its 500,000-SNP genotyping to $250. More heralds of the fast-approaching age of affordable genotyping.

Couples Select Embryos to Halt Inherited Cancer. Part of the NY Times’ series, “The DNA Age,” this article explains how preimplantation genetic diagnosis, or PGD, can avoid the tranmission of fatal conditions like Huntington’s Disease as well as significant cancer risk genes, as the family profiled in the article chose to do. This technology and the use of it raises ethical issues and has many talking about what it means that this technology may only be accessed by those with the significant financial means. The Times, as usual, has a balanced discussion.

Update: A Genetic Code for Breast and Colon Cancer. The first draft is in, and The Biotech Weblog has the scoop. This is very exciting! The promise lies in both detection (with tests like PreGen Plus) and with targeted treatment.

Technorati Tags: cystic fibrosis, clinical trials, genotyping, genetic testing, GeneChip, preimplantation genetic diagnosis, huntington’s disease, inherited cancers, breast cancer, colorectal cancer, diagnosis, treatment

For those of you interested in breast, ovarian and other women’s cancers, check out Breast Cancer Chronicles if you have not already. Lillie Shockney, R.N., M.A.S. is a nurse specializing in breast cancer and a survivor herself. Her blog provides ongoing information, support and an expert perspective. Recently, she’s posted important info for people concerned about inherited cancers:

• What’s Hereditary About Hereditary Breast Cancer? If you’re asking that question, please read this post.
• Gather Your Family History has helpful advice on doing just that. If you are considering getting a genetics evaluation, the more detailed information you have, the better.

Technorati Tags: breast cancer, ovarian cancer, women’s cancers, family history, genetics

I am thrilled to see discussion in today’s NY Times about the promise of genetic testing for drug metabolism. In particular, I’m excited to see mainstream media discussion of tamoxifen efficacy and genotype.

Much has been made of research published in the past few months regarding aromatase inhibitors — to what degree they prevent breast cancer recurrence, long-term survival, overall survival, and to what degree they’re better than tamoxifen (current studies indicate ~2-3%). That’s very exciting.

What you’re not hearing about, and which could take treatment decision-making to a higher level, is research into gene variants that may indicate who is likely to respond to tamoxifen and who isn’t. This could alter what we’ve previously thought of as tamoxifen efficacy rates. Gina Kolata explains and quotes Dr. David Flockhart, a leading researcher in this area:

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I’m a bit late in announcing this but the latest issue of Mendel’s Garden, the new genetics blog round-up, is up at Genetics and Health. A few of the selections about rare genetic conditions caught my attention.

Dr. Paul discusses an intriguing collaboration between dog breeders and human researchers. Batten Disease, is a rare genetic disorder that appears in both humans and Tibetan Terriers. The breed club has a DNA database for the dogs, and you can guess the rest — but you really should read Dr. Paul’s commentary about what a collaboration like this can mean for a rare disease.

Filipina Soul writes about a rare, recessive genetic disorder, maple syrup urine disease, and recent research that suggests high carrier rates (up to 1 in 100) among Filipinos. According to Filipina Soul, the researchers have also identified a unique founder mutation that causes the disease. Research such as this is exciting — it can make pre-conception carrier testing possible, not to mention how awareness of ethnic risk increases the likelihood of early postnatal diagnosis.

Over at Ideas for Women, Trisha has thoughtful commentary on a study I’ve been meaning to write about. Recently, the Journal of Clinical Oncology published a preliminary study suggesting that women with BRCA1 or BRCA2 mutations who are exposed to X-rays have a greater risk for breast cancer. (Trisha also reported on the discovery of a BARD1 variant that in combination with a BRCA1 mutation significantly increases cancer risk. This variant has been found only in European families to date.) This has nothing to do with rare genetic conditions, per se, but I share her perspectives about this research, how the media covers news like this, and how we as individuals make choices based on this.

Technorati Tags: mendel’s garden, genetic disorders, batten disease, tibetan terriers, maple syrup urine disease, msud, carrier testing, brca1, brca2, bard1, breast cancer, x-rays

Breast Cancer Chronicles’ has recent posts on preventive options and insurance considerations for women who carry a genetic risk for breast cancer (a BRCA1 or BRCA2 mutation).

“For women who are genetically positive, that is, who carry a gene that increases their risk of developing breast cancer, it’s important to take aggressive action to reduce your risk of following in your family member’s footsteps - or, as I like to say, of wearing her bra.”

Elissa, our clinical director, adds: Choosing to learn whether or not you’re a BRCA carrier is a very personal decision. If you are a carrier, the preventive choices you take are also very personal. As many of you may know, these decisions involve different things for different women - from sense of self, body, sexuality, youth, mortality, empowerment, fear, control, guilt and much more. In short, no decision surrounding BRCA is simple. Genetic counselors are healthcare professionals who can help women (and men) consider whether testing is right for them - weighing the pros and cons of testing, evaluating preventive options, and discussing implications for family members.

I like Lillie Shockney’s suggestion for handling the privacy/insurance issue, and think it is one that I will use if my mother tests positive:

“At $3400, it’s an expensive test. Some women pay out of pocket for the test up front. If the result is negative, they then seek reimbursement from the insurance company; if it’s positive, they never tell.”

Read more about who is at risk for BRCA1-2 mutations.

Technorati Tags: breast cancer, BRCA1, BRCA2, prevention, insurance, family risk, pros and cons

Thank you, Gina Kolata, for continuing to explain both the science and the personal dilemmas of breast cancer treatment research.

Increasingly, oncologists and researchers are focusing on the nature of the tumor itself — “tumor typing” — rather than the location of the tumor when recommending treatments. I expect that very soon, we won’t be diagnosed with “breast cancer.” Rather, we may have “estrogen-receptor positive, HER2/neu amplified, TOP2A amplified cancer located in the breast.”

In addition to HER2 status, estrogen and progesterone receptors, there are other biomarkers currently under study that may help us make treatment decisions.

Genes may also tell us about whether or not we will respond to the treatments indicated by tumor typing. Research is mounting that the effectiveness of tamoxifen depends on which versions of the CYP2D6 gene you inherit.

Stay tuned for more posts on genes and drugs, aka, pharmacogenetics. And a hat tip to Hsien for her latest post on genes and cancer risk.

Update: Read more current posts about tamoxifen here. Also, DNA Direct now offers 2D6 testing for tamoxifen response.

Technorati Tags: breast cancer, treatment, tamoxifen, genes, pharmacogenetics, CYP2D6

As someone with a strong pattern of hereditary breast/ovarian cancer in my family, it’s safe to say that I follow breast cancer news closely. Last month, there was big news from NCI about a study looking at tamoxifen and raloxifene for breast cancer prevention. Many trumpeted the summary findings — “raloxifene is as effective, with fewer side effects!” — but with studies like these, the devil lies in the details.

Denise Grady of the NYTimes dived into these details, and she breaks them down for us in her “second opinion” piece. This is the real news. Women making decisions about treating and preventing breast cancer are faced with a complex challenge of weighing risks, benefits, side effects, and peace of mind. Understanding the real details of your options — and figuring out what they mean to you, personally, can make all the difference in what you decide.

Technorati Tags: breast cancer, tamoxifen, raloxifene, drugs, prevention, treatment, side effects, STAR

When newspapers announce that a gene has been discovered for a certain disease — such as the recent findings of genes involved in chronic fatigue syndrome, schizophrenia, and obesity — we inevitably get calls from people interested in testing for that genetic finding. But “finding a gene” can mean a few different things.

Finding the gene: Sometimes, researchers identify a gene that definitely causes a disease, such as the discovery of the gene for hemophilia or cystic fibrosis. Such a finding does not necessarily mean that a genetic test is immediately available or that researchers can cure the disease. However, it does mean that the medical community may be closer to a possible cure. Knowing the genetic origin of a disease can aid in diagnosis.

Finding one of many genes: In other cases, researchers discover a gene that plays a role in a small subset of people who get a common disease, such as the genes BRCA1 and BRCA2, which cause breast and ovarian cancer in some people. Again, finding these genes puts researchers one step closer to a cure or genetic test that can help certain people with the disease.

Finding a gene in animals: One way to understand gene function in humans is to find and manipulate a gene that causes an animal — such as the mouse or fruit fly — to show symptoms similar to a human disease. Animals have genes that are very similar to our own, so these discoveries help point researchers to the biological function of a human disease gene. However, it is a long path from finding a gene in flies or mice to finding a genetic treatment for a human disease.

Technorati Tags: genes, genetics, genetic testing, DNA

The NIH is looking for sisters of women who’ve had breast cancer. Why? For one of the first long-term studies to look at how genes and environmental factors — homes, workplaces, and communities — affect women’s risk of breast cancer.

The Sister Study is exciting for a number of reasons:

• They’re enrolling 50,000 women. Such a large study will give more powerful results.

• They’re studying women from various racial and ethnic groups. Women of color have historically been underrepresented in research and have different risk issues. For example, African American women have higher rates of death from breast cancer.

• They’re studying women from different generations. By gathering information about jobs, geography and medical history, they can uncover about environmental factors and breast cancer risk over time.

If, like me, you Race for the Cure in honor of the women in your family – consider giving a bit more: give yourself. Participating by donating and advocacy is important, but partipating in scientific research is another. The progress of science depends on people participating in scientific research. So often, the people being asked to participate are patients or survivors. This is a great opportunity for us, the supporters, to give something truly valuable that can improve the lives of the generations to come. Thanks to Dr. Hsien Hsien Lei for drawing attention to the Sister Study and the importance of participation.

Read Sister Stories from study participants
See if you are eligible to enroll in the study

Technorati Tags: breast cancer, BRCA testing, DNA testing, genes, genetics, sisters, clinical trials

Tina in Arizona asked us by email:

“What does the latest news on genetic testing for breast cancer mean for me and my daughter? Two years ago, I had the test for breast cancer — the results were negative. Does this new research mean that my test was not accurate? Is there a chance I could still have a mutation?” I am a breast cancer survivor (diagnosed at age 48), and there’s breast cancer in my dad’s family.”

The simple answer, Tina, is that this new information does not make your test any less accurate. Your test, called full sequence BRCA testing, looked for genetic changes in two tumor suppressor genes (called BRCA1 and BRCA2) that are currently known to be associated with hereditary breast and ovarian cancer.

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