Unregulated DTCG saved my life.

Ok, so if Ellen Matloff hasn't flipped her bobbed haircut, 99245 without 60 min of MD care-insurance billing head yet, then this story will make her and the rest of the counselors who get mad when untrained MDs do BRCA testing flip out.

A woman's husband on DNADay takes advantage of 23andMe's rock bottom 99 USD fee. Clearly intended to double their database.....which it did

Only to have her HUSBAND open her results and

WHAMMO! You are a BRCA1 carrier! Mazel Tov! Not exactly the "fun" he had been looking for when he saw that flyer.....

Why does Myriad market to doctors? Their stance "We are missing a ton of BRCA mutations out there"

I agree.

So you would think I am happy that an unregulated DTCG testing company that the FDA pilloried finds a medically valid BRCA1 mutation that wasn't suggested by doctors.

Well, here's the shocker.

I am glad they found it.

Yes, thank god someone did before she had ovarian or breast cancer! If she would have, penetrance here is NOT 100% guys......

I am also glad that the woman who had the test was mentally stable enough and smart enough to seek professional help. I wonder what her husband and her do for a living?

I wonder if they are college educated. I wonder if there demographic is anything like the majority of the United States.....probably not....Oh wait. Princeton Grad, Prior Google Grad, CEO....yeah sounds just like my cousin Billy in Dushore PA (FYI I don't have a cousin Billy) But Dushore is in BFE.....

I am not glad that everyone is NOT like Mrs. Steinberg or her husband. In the right hands and with easy access to health professionals this works, sometimes........That is why the FDA has stepped in. Not everyone lives like the Steinberg's

Without professionals and without a level head, this could be a problem.

But the news story re-emphasizes what is crystal clear. This is an unregulated company that delivered a medical diagnostic. This result then drove clinical decision making.

Seriously. The DTCG BRCA test is a medical test. I think the FDA gets that part. Despite what DTCG says.

The Sherpa Says: I am happy for this woman. We need more testing, I agree with Myriad. I also think CGCs should be out teaching doctors rather than letting pharma reps do it. In fact excellent CGCs like Ms. Matloff should never see patients and should instead teach doctors how to do cancer counseling everyday. That is what is needed here, more education given to those who need it. Because clearly the doctors who told Mrs Steinberg (I assume she is AJ) that she wouldn't "need" genetic testing despite the family history of cancer are likely in need of some schooling.

End of Gene Patents?

With the NY district court ruling in ACLU et.al. v USPTO/MYGN it appears clear that the bar for gene patents is super high and most will likely not reach it. Does this mean the end of gene patents or even just the BRCA1/2 patents?

No, but it is the beginning of slipshod sequencing and a whole host of labs testing for BRCA1/2 sequences. It is also the making of a SCOTUS case.

But here's why I think Myriad STILL is the gold standard.

A. They have the experience doing this testing
B. They have the infrastructure to handle national samples
C. They have the ability to analyze rare variants best. Why? They have the samples.....

That being said, could Quest or LabCorp begin BRCA testing? Yes and they would do a hell of a job.

One thing is for certain, Myriad will have a hard time justifying that 3120 USD price tag.

If you have MYGN maybe a short is in store?

The Sherpa Says: Myriad is how a genetics lab should be run, except for the outrageous price.

Stand Up To Cancer!

Let's Join together and beat cancer down! As I posted earlier about Christina Applegate and now about Mia Perovetz. Cancer can destroy families. Why not stand up to it. That's what celebrities are doing tonight. My friend Walter recently posted on this.....you can see it Here!

We have to beat cancer! Tune in tonight September 5th, at 8:00 pm EST and PST, ABC, CBS and NBC will donate one hour of simultaneous commercial-free prime time for a national fundraising event. Tune in donate and let's stop cancer in its tracks!

Christina and Jessica beat BRCA1

I certainly hope my friends at Speigel and Grau get in contact with Christina Applegate. As I suspected and mentioned on August 7th......It seemed, based on the limited family history I had, that Christina Applegate was a BRCA carrier. Today, I find out I am correct.

This is timely news as Helix Health of Connecticut is now releasing the CliniCast from May 21st 2008: "How Genomic Medicine is Changing the Management of Breast and Ovarian Cancer". Interestingly, this was the day which GINA was signed into law. In fact it happened right when Jessica Queller announced to the world that doctors who are "too old" to learn genetics should retire.

Well Jessica, I am here to teach those doctors.....If they don't want to learn, then I agree. They should retire.

If you want to learn more or even take a listen to our CliniCast, you can pre-order them here.

In addition, if you are listening Christina, you can get a copy today. Just email me at thegenesherpa@gmail.com

Ms. Applegate is scheduled to appear on a one-hour TV special, "Stand Up to Cancer," to be aired on ABC, CBS and NBC on September 5 to raise funds for cancer research. I am looking into how I can help with this fantastic fundraiser.

The Sherpa Says: BRCA is scary, breast cancer is even scarier. When you know your risk, you can detect disease early and even prevent it in the first place. That is the definition of Personalized Medicine.

Burrill Report....deCoded

Consumers are worried about developing genetic based diseases, but remain reluctant to use genetic tests that will provide early warning signs.





That is the lead statement in the executive summary from the Burrill and Company Personalized Medicine and Wellness report issued last week. Many may ask "What's this report have to do with me?" many have even doubted the validity of the report in favor of the blogosphere......In the arena of Genomic Medicine, I would say the blogosphere is pretty one sided.....IN fact, that is why the Sherpa is popular. Until I started blogging, this place was pretty much a mutual admiration society. Further proven by the backlash I received when I said that governmental regulation was coming and then came.


So let's go back to the poll.....


Second Line

Companies need to make the case for the benefits of testing, allay privacy concerns, and would be wise to work through doctors.


We have known this in Medical Genetics for a very long time. If you have counseled anyone, you know these concerns to be true.....


Only one in five consumers said it was very likely (5 percent) or likely (15 percent) that they would get a test in the next few years to measure their genetic risk for certain diseases.


This is a point of contention between Daniel and Me.......He says 20%......I say 5%....


Why? Only the very likely will get the test. It is just like a referral to see another doctor.....if you aren't feeling ill, only the very likely will ever go see that specialist.....It is called the attrition rate and is commonly understood in medical care......only 20% of your "presymptomatic ill" ever go see the referral.


So, I remain certain, the market for these tests is 5%

Just 4 percent of those surveyed said they have ever had a genetic test to determine their risk for a particular disease, but two-thirds of those who did so because it was recommended by a doctor.


My guess is that these patients received BRCA testing. What this doesn't say is who ordered the test and was it done DTC versus through a physician. Did the other one third "Ask" a physician for the test? The most likely reason a physician orders a genetic test? You Guessed it "Patient Request"


I don't believe all of this self reported survey (Physicians never like to look out of the loop) but the most likely reason to test is pretty strong.


Factors associated with ordering or referring included practice location in the Northeast [odds ratio (OR), 2.30; 95% CI, 1.46-3.63%],


feeling qualified to recommend CSTs(cancer susceptibility tests ) (OR, 1.96; 95% CI = 1.41-2.72),


receiving CST advertising materials (OR, 1.97; 95% CI, 1.40-2.78%),


and most notably, having patients who asked whether they can or should get tested (OR, 5.52; 95% CI, 3.97-7.67%).


It Trumps Feeling Qualified!!!! Even Myriad knows this!


So with this in mind, let's go back to the Burrill Report.


What About GINA????

only just over a quarter of respondents (28 percent) said the passage of GINA made it significantly more likely (7 percent) or somewhat more likely (21 percent) that they would undergo genetic testing. A total of 68 percent said the passage of the law would have no effect on their decision to get a genetic test.


Remember the rule of attrition......that to me states only 7 percent feel more likely to test.....But the physician recommendation may alter that a little bit....not alot, but a little. We saw a spike at Helix Health of Connecticut....so I know this must be influencing some....


SO Who did the report?

The survey, conducted through ChangeWave’s proprietary network between May 27 and May 30, 2008, is based upon responses from 550 consumers.


AND THE NETWORK CONSISTS OF?????

Nearly 3 out of every 5 members have advanced degrees and 93 percent have at least a four-year bachelor’s degree. This is a proprietary network of more than 15,000 highly qualified business, technology, and medical professionals in leading companies of select industries—credentialed experts who spend their everyday lives working on the frontline of technological change.


IS THERE MORE TO COME?????


These results represent the first part of a three-pronged benchmark personalized medicine and wellness survey that is being undertaken by Burrill & Company. Companion surveys of physicians and industry professionals will be joined with this study for the final report, which will be made available this summer.

I found this article in 2007 by David Ewing Duncan very useful. The Quote from Lee Hood and then from David Altshuler both physicians.....

David asked Lee who has met with Google and has long been a maverick bridging the worlds of biology and I.T., "do Web entrepreneurs truly understand the limitations and pitfalls of this science?"

“They absolutely do not,” Hood says. “The heart of predictive medicine is in getting clinical validation and working out the fundamental biological systems—how genes and proteins and other elements interact. I don’t think that most of the Web 2.0 crowd entirely gets this.”

The he asked David what value do you see?

Critics also see little value in testing healthy people for a wide range of possible diseases. “We don’t take an M.R.I. for everything, and I don’t order every test for every person,” says Harvard geneticist and physician David Altshuler, a key figure in the Human Genome Project. “Those who do are scamming people. It’s the idea that just knowing something is useful—well, maybe, maybe not.”

I wonder what the physicians poll will show????

The Sherpa Says:


The writing is on the wall....Despite what the blogosphere says.....if these guys have 15000 members, why poll just a paltry 550? Because all they needed for an effective sampling WAS 550....We are not talking about a study to establish linkage here ladies and gentlemen...we are talking polling....much like political polling they only need a good sample....unlike(No offense) the skewed sample in the blogosphere. To Industry I say, get to know your doctors. There is a reason why Myriad is so successful......

Jessica Queller and BRCA1

First I would like to apologize to Spiegel and Grau. I missed you gracious letter. Please give me a call.


Second.....I am catching some serious heat about the deCode rant! I never knew so many smokers were hoping to escape cancer and angrily flaming me with emails. Here's a hint ladies and Gentlemen........Quit Smoking and maybe you will avoid cancer. To all of those who decided to fill my gmail yesterday....thanks for reading this blog. I appreciate your interest.


I don't know how many of you picked up the USA Today on March 31st, but in it was a profile on Jessica Queller. She has written a book called:

Pretty Is What Changes-Impossible Choices, The Breast Cancer Gene, and How I Defied My Destiny

About the Book....
Eleven months after her mother succumbs to cancer, Jessica Queller has herself tested for the BRCA “breast cancer” gene mutation. The results come back positive, putting her at a terrifyingly elevated risk of developing breast cancer before the age of fifty and ovarian cancer in her lifetime.
Thirty-four, unattached, and yearning for marriage and a family of her own, Queller faces an agonizing choice: a lifetime of vigilant screenings and a commitment to fight the disease when caught, or its radical alternative—a prophylactic double mastectomy that would effectively restore life to her, even as it would challenge her most closely held beliefs about body image, identity, and sexuality.

The Sherpa Says:
To understand the human issues surrouding genetics we need to experience or read others' experiences. I think many of you already know of my family's history.....very similar.
I am hoping to invite Jessica to the blog. Wish me luck.....

This week in NEJM

So I have been reading about how the new article in the New England Journal of Medicine shows that BRCA gene mutations are not worse than sporadic breast cancers due to non-BRCA mutations.

If you look at the article you will see that there are many reasons why this is flawed thinking. But more importnatly it flies in the face of another study which actually showed and increased risk in worse outcomes with BRCA1 mutations.

So on closer inspection what was the NEJM article about?

They took all breast cancer specimens available in Israel's National Healthcare repository and looked for 3 I repeat 3 FOUNDER MUTATIONS....... This immediately makes the study invalid to comparison on women who have non ashkenazi mutations, especially if they are not founder mutations.

Secondly they analyzed outcomes retrospectively. This is a notorious way to get confounding results as well.

Thirdly this study did not have interpretable data regarding estrogen or progesterone receptor status.......This is a big deal!!!

And Lastly,
"We had 16-year follow-up data on mortality and incident cancers, but information on the cause of death was available from the Central Bureau of Statistics only for deaths that occurred before 2000." None from after 2000........

The Gene Sherpa Says: Before bloggers and press go off half cocked in this interpretation we need to be careful in how we evaluate this study. This ONLY means if you are an ashkenazi jew from Israeli heritage and have one of 3 founder mutations, then you are not more likely to have adverse outcomes than ANYONE else who is Israeli and Ashkenazi with non founder mutation breast cancer....That's IT. Nothing else can be extrapolated here. To those who are.....tread carefully...Because you are misleading the public!

Direct To Physician Testing... Myriad re-enters the fray.

According to my insider sources it appears that Myriad is going to launch a Direct To Consumer testing campaign for Hereditary Breast and Ovarian Cancers. Their quote is:

• "Because 1 out of 10 patients in your practice may be at risk for hereditary breast or ovarian cancer....Help Turn the Tide"
  

What happened the last time they campaigned? Demand for counseling went up 244% In addition there is a significant amount of literature that indicates the number one reason a "non-geneticist" orders a genetic test is patient request.

There are several ethical issues that need to be addressed with direct to consumer testing.

• A number of these tests lack data on their accuracy and reliability, making interpretation of results difficult.
• DTC genetic testing is undertaken outside the context of the physician-patient relationship and may lack appropriate individual and family genetic counseling,
• This often is leaving the consumer vulnerable to potential harms, such as misinterpretation of results, including false positive or false reassurance, with limited or no benefits

There are several solutions to these problems. None of which should exclude a trained health professional. Remember what I said before "beware the doctor peddling genetic tests"

The Gene Sherpa says: New York in October, the Avon Breast walk, Myriad and its DTC brokers will make some serious cash. Please make sure it is not at YOUR expense. Get the right follow up, get the continuity of care, and BEWARE NON-GENETICISTS SELLING GENETIC TESTS!

Mammography at 40

Recently the American College of Physicians (The Organization of Internal Medicine/ACP) released guidelines regarding mammography at 40 years of age. Until now the ACP guidelines were everyone 40 and over gets mammography. There is very little good literature that supports this previous recommendation, yet the American Cancer Society, ASCO, and ACOG still recommend that every woman 40 and above gets a mammo every 1-2 years. The ACP found that in their analysis the conclusion was "Although few women 50 years of age or older have risks from mammography that outweigh the benefits, the evidence suggests that more women 40 to 49 years of age have such risks." After reading the study and looking at the guidelines, they are not that drastic. Key Point Include

• Women 40-49 should have routine risk assessments for breast cancer risk. What is increased risk?
• 2 first degree relatives with breast cancer
• One with breast cancer and a previous breast biopsy(the patient)
• Previous breast cancer
• Previous noncancerous breast gland changes(DCIS, atypical hyperplasia)
• Prior chest irradiation (for cancers/not for a chest xray)
• BRCA1 or 2 mutations or family members with these mutations
• Physicians should inform these 40-49 year old women of the risks and benefits of mammography. What are the risks?
• False positive results (never shown to cause psychiatric problems:anxiety, depression etc.)
• Radiation exposure
• False reassurance from missed tumor
• Clinicians should base their screening mammography decisions on the woman's preference and risk profile.

The Gene Sherpa says: If you are younger than 50 mammography should be a collaborative choice between the physician and the patient. The problem?....When has a physician used a risk assessment tool to evaluate a patient for breast cancer? Sure cancer geneticists do this. But Internists? Sounds like we need some education for the internist, and for the patient. Would you get the mammogram?

Pancreatic Cancer miRNA This week in JAMA

Earlier this month an article in JAMA studied the expression pattern of miRNAs (microRNA) in pancreatic cancer. What they found was pretty important.
From Medical News Today May 5th 2005

"Pancreatic cancer is a lethal disease, with the annual deaths nearly equaling the incidence of 33,000 in the United States, according to background information in the article. In humans, aberrant expression of miRNAs contributes to carcinogenesis by promoting the expression of proto-oncogenes (a normal gene that has the potential to become an oncogene) (a gene that can cause a cell to become malignant) or by inhibiting the expression of tumor suppressor genes"

From JAMA 2007 May 2;297(17):1901-8

CONCLUSIONS: Pancreatic cancer may have a distinct miRNA expression pattern that may differentiate it from normal pancreas and chronic pancreatitis. miRNA expression patterns may be able to distinguish between long- and short-term survivors, but these findings need to be validated in other study populations.

Expression of miR-196a-2 was found to predict poor survival (median, 14.3 months [95% confidence interval, 12.4-16.2] vs 26.5 months [95% confidence interval, 23.4-29.6]; P = .009).

What does this mean? It means we may very well be on the way to the predictive part of personalized medicine in pancreatic cancer. Obviously replication needs to be accomplished.

But the results were pretty convincing as far as statistic goes. By predicting survival time we can help the patients and their families with this horrible and most often fatal cancer. More importantly perhaps this signature pattern may allow us to develop molecular therapies to target the tumors associated with the worst outcomes.

The Gene Sherpa says: If you have family members with early breast cancer (younger than 50) you may be at risk for pancreatic cancer. You should speak with your doctor about having genetic counseling.

Breast cancer and genetic discrimination, relics of the past

Sorry so long since the last post.
2 MAJOR things came across my radar yesterday. Unfortunately I was giving a lecture on DNA Day to some medical students, so I could not post. Without further ado

Number 1 Congratulations to The United States House of Representatives, they finally passed GINA. If you don't know, this bill has been trying to be passed in some form or another for over 10 years. Some say that this is one of the major limitations to everyone getting their genes tested. Even the Harris Poll from 2002 documents this. So what does that mean for genetics.....Well, it is on to the Senate, where in 2005 a form of this legislation passed unanimously. Given the department of health and human services/Presidential push for Personalized Medicine it is likely to become a reality this year.

Number 2
Given the atmosphere in the US, there seems to be a similar push in the UK. This time it is for pre-implantation genetic diagnosis and breast cancer. Yes I agree a horrible disease and personally I feel that we must have early detection and prevention of breast cancer. In the UK there is application being presented to the Human Fertilisation and Embryology Authority to test for BRCA1 in embryos. What do you think? Is this technology going to come to the US?

Gene Sherpa says.....REI specialists very often do not have training in Medical Genetics per se. That makes me a little leery. Especially when they have yet to standardize the medium in which they grow the embryos. Why is this an issue? Because environment plays a key role in telling DNA what to do. At the same time, to prevent other cancers it is already being done in the US.