NCCN Decision

Here is the NCCN decision on whether to add HERmark:

(Side note: HERmark is a technology developed within the past decade – as opposed to one developed in the 1950’s as is the case with IHC – and is an alternative option for medical professionals trying to give women with a new diagnosis of breast cancer the proper medication. It is the modern age of personalized medicine and the entire purpose of this blog.

NCCN decides to stick with IHC & FISH/CISH. They balk at a chance to lead the upgrade to better technology for women with breast cancer. Their explanation is “that’s what ASCO is doing”.

What that means is physicians (and families) now have fewer options when considering HER2 targeting agent, or whether to consider toxic  chemotherapy as the only current option (or clinical trial with something in the pipeline, of course).

October Update

Just in case anyone has been waiting with baited breath for an update, here you go: the NCCN (National Comprehensive Cancer Network) breast cancer panel met in late July, 2014 to discuss updates to their breast cancer guidelines. With the help of various high-level scientists, I successfully persuaded a megalith in the US reference lab industry to submit a “change request” to NCCN.

The submission asks NCCN to consider HERmark, a fascinating technology that identifies women who are eligible for a drug called HERceptin, as an alternative to IHC and FISH/CISH – technologies currently used to identify a woman’s ability to use Herceptin and other HER2 targeting agents.

Here’s the kicker: IHC & FISH/CISH are known to be wrong at least 20% of the time yet are the standard of care all around the world for this subset of oncology testing, and current medical reimbursement standards reward physicians, hospitals, clinics and pathologists to continue running these flawed technologies.

If NCCN mentions HERmark as a possible alternative as a result of their meeting in July, even only in the off-chance of an “indeterminate” IHC/FISH call (meaning IHC and/or FISH fail to identify the patient as being eligible nor ineligible…the purgatory of HER2 decisions, crucified by terrible, outdated technologies), as many as 40,000 women every year could have an improved life expectancy by being given the proper combination of drugs.

Much weighs in the balance of the NCCN decision, and word on the street is that the update is expected sometime during the month of October.

What a coincidence, NCCN decides the fate of women with breast cancer during the same month that the NFL and countless organizations around the world make a killing by claiming they’re out to save the tatas.

Let’s hope NCCN is out to save some tatas by improving the technological options of women diagnosed with breast cancer. Help spread the news, the oncorevolution is set to begin!

Improving Breast Cancer Diagnostics

In case this is the first time you have read this blog, I encourage you to read the very first post way back at the beginning then return here to better understand what this is all about. If you want to get angry, also read the one that describes why 1941 = Ungood.

In three weeks time the National Comprehensive Cancer Network (NCCN) will meet to discuss breast cancer guidelines. One specific subset of breast cancer testing is acknowledged as being flawed upwards of 20% of the time, and the two technologies that are approved by NCCN in this realm are also not shown to be any better than the other.

That is, a well-recognized governing body that gives guidance on how oncologists & pathologists should determine a woman’s course of cancer therapy – and thus both her life expectancy and her quality of life – blatantly admit that two approved technologies are wrong at least 20% of the time, and that neither is any better than the other.

My mission is to attempt to improve this clear inefficiency.

The purpose of these two flawed technologies is to define a woman’s eligibility for drugs that bind to specific receptors on a breast cancer tumor cell. By binding to the specific receptor, the drug controls the growth and proliferation of cancerous tumor cells.

If you have ever heard of the term “HER2-negative”, that means a woman cannot use a HER2 targeting drug like Herceptin. HER2-negative also means that a woman has much fewer treatment options. Getting a woman’s “HER2 status” correct is imperative.

Getting it wrong 20% of the time is the current standard of care.

I discovered a technology developed by a biotechnology company in San Francisco that is much more sophisticated in determining whether a woman can benefit from these HER-2 targeting agents. HER stands for Human Epidermal growth-factor Receptor, by the way, and #2 just denotes that the drugs bind to one particular receptor out of 4 possible receptors (HER1, HER2, HER3, HER4).

The more sophisticated technology that I discovered is called HERmark, and it has been available since 2008. The scientists who developed this technology have published paper after paper on the clinical implications of this technology, and yet the company that developed this assay suffered the consequences of capitalism: they don’t have a sales force because they are financially strapped. The technology never took hold in the market, and oncologists continue to rely on technologies that are wrong 20% of the time.

With over 220,000 newly diagnosed breast cancer patients every year, a 20% error rate is mind-boggling. Imagine if GM had a 20% error rate when they produced cars in their manufacturing plants (oh wait, they already do). The consequences of this rate of failure are catastrophic when we are talking about people’s lives.

About two months ago I began networking within the company that developed the HERmark assay and successfully convinced the scientific team to submit a request to NCCN to change their breast cancer diagnostic guidelines. NCCN will meet for 2 days between July 20-22nd, and at that meeting the NCCN panel will determine whether HERmark is a suitable alternative to the current standard of care for assessing whether a woman can benefit from HER2 targeting medications. Note that I say alternative, not replacement.

The pharmaceutical companies that conduct clinical trials for HER2 targeting medications continue to only use the out-of-date technologies in the trials that lead to the approval of their medications. This is the part that grinds my gears. HERmark can never supplant the current standard of care because HERmark has never been used at the beginning of a clinical trial to screen patients for HER2-targeting therapies – otherwise known as a prospective clinical trial. Retrospective analyses, or backwards looking data analysis, has shown that HERmark is significantly more accurate at predicting treatment outcomes.

This is not difficult to understand, though. If a technology is flawed 20% of the time, very often patients will be put on a medication when it should not have been given because the drug will have no benefit. The more sensitive & specific a technology is, the more beneficial the treatments become. This is the basic concept of personalized medicine – the right medication for the right patient at the right time.

We should not put the entire population on antibiotics, only those patients who have bacteria that will respond to the specific antibiotic in question. That same principle applies to HER2 targeting drugs: only patients who will respond to these drugs should be given the drugs, and accurate testing is critical if the goal is to save lives.

Help save a life. Join the OncoRevolution. Let’s see if we can help sway public opinion prior to the start of the NCCN meeting on July 20th. Or are you willing to roll the dice should you or your loved one be diagnosed with breast cancer?

Heck, 20% wrong means 80% right!

A quick update on progress

For those who have followed this blog, I wanted to give a brief update. Through tedious networking I was able to persuade the medical teams within both Monogram Biosciences & Laboratory Corporation of America to submit a guidelines change request to the National Comprehensive Cancer Network (NCCN).

The submission will request an update to current HER2 testing guidelines – guidelines for testing that is known to be flawed upwards of 20% of the time. This guidelines-change-request will ask the NCCN advisory committee to review a new HER2 technology, known as HERmark, and ask the committee to address whether this is a valid supplemental tool for the oncology-treating community in determining a woman’s ability to use HER2-targeting agents.

This may all sound like mumbo-jumbo, but realize that with over 200,000 newly diagnosed breast cancer patients every year, getting the wrong result 20% of the time with current technologies means that over 40,000 women are either deprived access to life-saving medications or are being exposed to agents that are expensive and ineffective – every single year in the US alone. The global implications of faulty HER2 technology is breath-taking.

HERmark has the ability to improve patient quality of life, provide more accurate information to physicians and families, and potentially save a ton of money in long-term financial costs that are associated with disease progression in cancer (when improperly diagnosed and given wrong medications).

The tricky part is that the submission needs to be received at least 3 weeks prior to the July 20th NCCN meeting, and apparently the documents need to go through a team of lawyers within a ginormous, multinational corporation with the thickest of bureaucratic red tape. Let’s hope LabCorp does the right thing and expedites this request.

I’ll write an entirely new post over the coming days explaining the submissions, the bar that needs to be surpassed, and the clinical impact of a positive outcome.

Mayday: the business of breast cancer

I think it’s interesting that the holiday that praises international workers on May 1st – one that is a loose nod to communism/socialism –  is also recognized as an international distress signal.

Mayday, mayday: breast cancer HER2-diagnostics is a racket.

This week I learned about TC/PC, otherwise known as “technical component/professional component”. This simple acronym explains why breast cancer HER2-diagnostics are presently in the dark ages.

TC/PC is laboratory-speak for “reimbursement for highly skilled services rendered”. Technical Component (TC) allows a local laboratory, Lab A on 50 Main St, to get reimbursed for preparing an IHC/FISH breast tumor sample. Professional Component (PC) enables the send-out hospital, laboratory, surgery center, or oncology clinic to get reimbursed for the interpretation of that IHC/FISH sample since someone has to look under a microscope to make a subjective determination of the patient’s course of therapy.

TC/PC is how the oncology-treating community gets reimbursed for using IHC & FISH methodologies (the ones that are stated in the guidelines as being incorrect upwards of 20% of the time) to assess a woman’s ability to use HER2-targeting monoclonal antibodies.

However, in January, 2014, the reimbursement for TC/PC was cut considerably under the Affordable Care Act, otherwise known as ObamaCare.

I visited a message board recently that was discussing this topic of reduced reimbursement for TC/PC, and the authors of the statements on that board were presumably either oncologists or pathologists. The uproar in the chat room was all about how much these TC/PC reimbursement cuts were going to affect the pocketbooks of said disgruntled authors.

Anecdotal reports describe reimbursement cuts from around $200 per IHC/FISH tumor sample down to about $50 bucks. That, my Fellow Readers, is what I would call “profiteering”.

I would also call it downright dirty money.

Why is it dirty? Because these clinics/pathologists/hospitals are choosing to run IHC/FISH through a local laboratory – a decision that everyone knows can generate incorrect values upwards of 20% of the time (a conservative estimate, I’m sure) – for the sole reason that these local laboratories enable the clinic to get reimbursed for the “Professional Component”, or PC reimbursement procedure code.

Look it up. I’m not making this up, folks. Now let’s take an even further dive into this farce:

There have been numerous studies documenting how a “Local Lab” is less efficient at getting accurate IHC/FISH results when compared to a “Central Lab” because of various degrees of quality controls. To put this in layman’s terms, a “local lab” is Lab A on 50 Main St, and a “central lab” is a well-recognized lab that is publicly traded on Wall Street (the one that sends you bills in the mail).

In honor of Mayday, this is where I will confess that I don’t see any difference between “local” & “central”. Both are capable of performing what’s called an “in-house brew” of IHC & FISH, and both local & central rely on a subjective pathologist’s retina/glasses/mental acuity to determine the outcome of IHC & FISH (and thus a patient’s course of therapy/livelihood).

That, my Fellow Reader, is exactly why IHC/FISH is only capable of achieving reproducible results 80% of the time.

My honest opinion is that the idea of “central lab is better than local lab” is just a big marketing ploy by the central lab that has sufficiently deep pockets to make that bold of a statement. However, it is accepted as fact among the oncology/pathology community that “central is better than local” when determining HER2 status with IHC/FISH (and yet these samples are still being sent to local labs, can you believe it? Why you ask? Because the central lab gets reimbursed on both TC & PC, whereas the PC reimbursement goes to the clinic/pathologist/hospital if the tumor sample is sent to a local lab. Outraged yet? Join the OncoRevolution).

So back to the point of the story, what is the business of breast cancer? An oncologist/breast surgeon/hospital/pathologist has little-to-no incentive to get a HER2 result correct – the incentive is to get reimbursement from an insurance company for the PC fee schedule.

Mayday, mayday: Welcome to crazy (or “kray-kray” for short).

So what incentive would a clinic/pathologist/hospital have to send a breast cancer tumor specimen to a specialty, high-science biotechnology company that can quantify HER2 protein expression?

There’s no incentive at all!

That high-science biotech company would perform the entire HER2 assay itself, and wouldn’t allow the clinic/pathologist/hospital/central/local lab to get reimbursed for the Technical Component nor the Professional Component.

To sum this up: first an IHC sample is sent to a local lab, and the pathologist/hospital/clinic gets reimbursement for the PC (subjective) interpretation of HER2 status (and thus a patient’s treatment options and survival outcome); then if there is some concern of accuracy, the pathologist/hospital/clinic will request that a FISH assay be performed and again, there is reimbursement for the “professional component”. Finally, regardless of these 2 outcomes, no one is ever considering that both IHC & FISH are wrong upwards of 20% of the time, and that the results of both of these assays are entirely subjective/flawed.

The ASCO/CAP guidelines explicitly describe IHC & FISH as being incorrect upwards of 20% of the time, and yet where are the guidelines that expose the fraud of breast cancer HER2-diagnostics?

In this twisted capitalistic society we live in, a patient’s livelihood and her health outcome is less important than making a buck on the treatment decision-making process.

Mayday, mayday: this business is killing us.

Meeting adjourned.

 

National Comprehensive Cancer Network

To anyone following this story, I wanted to quickly share some great news: the NCCN meets this July 20-22 to review updates to their guidelines for all things Breast Cancer. Submissions must be made at least 21 days prior to the meeting, and below I have indicated how they score the evidence provided upon submission.

This is so exciting, given all the data out there I cannot imagine that HERmark will not at least clip the 2B mark for addition to their guidelines, but clearly a Category 1 outcome would pave the way for improved oncology diagnostics worldwide.

Mini victory for sure, now comes the tough part: convincing Monogram Biosciences to submit a guideline change request. More to follow…

“NCCN Categories of Evidence and Consensus

• Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
• Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
• Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
• Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.”

http://www.nccn.org/about/submissions.aspx

Garbage In, Garbage Out

It was probably at some point in my 20’s that I understood the concept of “you are what you eat”. Call me slow, but I finally figured out that eating burritos/pizza purchased from a gas station and heated in a hazmat microwave – for breakfast – was a bad idea.

Next I remember walking through a museum in London (it likely was something less exotic, like St. Louis) that described improvements to the body’s overall health at each time interval after one stops smoking: after 30 days your sense of smell improves; at 90 days your taste buds function better; at 3 years your circulation returns to normal; at 10 years your risk of death or slightly less than had you never started smoking. I’m clearly making the specifics up, but Dr. Google will fill in the missing blanks for those interested.

Now think about oil spills in Alaska and in the Gulf of Mexico, and all the little fish that feed the larger fish that are then served on our dinner plates at fancy restaurants across the country. Or at Micky D’s & Kantucky’s, more likely. One nugget of wisdom I learned recently is that dates, those sweet jewels from mother earth, attach to heavy metal ions as they pass through your intestines, ridding your body of chemicals such as mercury, for instance.

The point of all these anecdotes is that everyone reading this can make the logical link between input and output. You put bad things into your mouth, your body feels bad as a consequence (hello, hangover). You put bad info into a computer algorithm, wrong information comes out the back.

The predictive value of any oncology diagnostic is only as good as the technological sophistication of the methods being used. For anyone who has read previous posts, is interested in science, and wants to change the world, let’s now explore IHC & FISH…

IHC & FISH are the two standard of care methodologies used to determine if a woman diagnosed with breast cancer is a candidate for some of the most modern drugs on the market today, known as monoclonal HER2-targeting antibodies. The result of the IHC/FISH assays also gives the physician valuable information about the patient’s prognosis, ie whether he/she is facing an aggressive form cancer.

Seems like pretty valuable technology, if it were my family member who was being treated, I would certainly be interested to learn the outcome of this IHC/FISH result (tongue-in-cheek; I would demand that my doctor use more advanced technologies).

IHC is a relatively inexpensive technology, around 200 bucks, and is most commonly ordered for breast cancer tumors. To simplify the science, IHC stains the proteins found on the tumor cell and a pathologist looks under a microscope and makes a subjective assessment of whether he/she is seeing lots of HER2 proteins, or few HER2 proteins.

If he/she is unsure, the result is “equivocal”, or “beats me”. For anyone who read my previous posts, remember that Lab A will only get the same answer as Lab B ~80% of the time – for the same patient’s tumor drawn on the same day under the exact same circumstances.

Talk about garbage in, garbage out. It gets worse though, in case you weren’t incensed enough with just that level of subjectivity.

Not only is the “reproduceability” of the IHC assay only 80%, but inherent flaws of the assay also lead to improperly stained HER2 proteins in the first place. Finally, after a pathologist looks under a microscope he/she has the inauspicious task of determining whether this woman has aggressive breast cancer, and whether he/she will be denying access to potentially life-saving treatment. Sounds like wild guesswork to me. I’ll even take it one step further and call it: Cowboy Medicine.

So the pathologist doesn’t want to go out on a limb and he gives it a 2+ IHC score, which means “I don’t know” or scientifically “equivocal”. In 99% of all scenarios, this biopsy sample will then automatically trigger a FISH analysis. Let’s now dive into FISH…

(For those reading this far, anxious to know what these acronyms stand for here you go: ImmunoHistoChemistry & Flourescent In Situ Hybridization. Now aren’t you glad I didn’t mention that previously? Don’t even worry about what they mean, from now on let’s just say IHC is Incredibly-unHolyCrap and FISH is downright FISHY.)

As to FISH, let’s expose the fraud once-and-for-all: it is a ratio, plain and simple. It is a ratio of DNA. But wait a minute, aren’t we trying to find out if a HER2-targeting agent will work, and isn’t HER2 a protein? Why is FISH looking at DNA if HER2 is a protein? I hope at least a few of my readers don’t click away at this biology sarcasm, but the point is FISH is looking at a breast tumor’s DNA, and then makes a prediction of HER2 protein expression.

Remember: garbage in, garbage out. Predictions based on flawed assessments are totally flawed at the end of the day. Back to FISH, it gets worse…

So everyone now understands that FISH is a ratio of DNA, but in any ratio you need 2 items to compare, right? Good on the two of you keeping score!

So what is the denominator, if tumor DNA of predicted HER2 expression is the numerator? Here’s where I even lose myself in the science: the denominator is what’s known as a “centromere of chromosome 17”. But don’t even worry about it, we don’t even need to know what that means, does or says for now. Just trust me on this, you’ll be able to solve this riddle without knowing DNA from proteins from centromeres from s’mores crunch bars.

After the pathologist who said “I don’t know” to an IncredibyunHolyCrap result, another pathologist is looking into yet another microscope and is ready to make YET ANOTHER subjective call. I’m shocked, join the revolution.

In this subjective call, he/she is literally counting up little specs of fluorescent dots. It’s easy though, because they’re either red or green. The pathologist is counting up the red dots, and dividing by the number of green dots – and voila! Patient prognosis and drug options at your service.

But hold on a second, does FISH find every single DNA cell in the breast tumor? Not a chance, there would just be a big glow under the microscope in that scenario. FISH is looking at a subset of maybe 1% of the tumor, and making a prediction of the entire tumor. Fascinating, no? Or is that what we humans would describe as appalling?

So now what if the FISH pathologist counts 12 reds and 12 greens? That would be HER2 negative, since the ratio is a 12:12, also known as 1 for us math wiz’s. In this case the patient will not be given the drug Herceptin, since this patient is found to not have many HER2 proteins (remember though, FISH is looking at DNA, not proteins; quite the stretch of logic, but there it is).

So what if a different pathologist looks under the same microscope for the same patient at a  lab directly across the street? Consider this scenario: he/she now counts 2000 reds and 1900 greens. “Holy canoly, that’s a lot of reds…but that’s also a lot of greens. Divide and carry the one…the ratio is 1..05”. In this scenario, the patient is also deemed to have a HER2-negative tumor, and the patient is denied access to potentially life-saving treatments.

Now I’m no math genius, but 2000 looks to be a lot more than 12 in my mind, so how can these two results provide the exact same clinical outcome? Could it be a function of garbage in, garbage out? For anyone keeping up, the red dots are DNA that are thought to code for HER2 expression. Lots of red dots tells me there is a lot of coding going on, so simply taking a ratio of DNA could lead to totally arbitrary results.

And what are those results? Apparently only 50% of patients respond to Herceptin, and the entire scientific/pharmaceutical community is wondering why and desperately trying to find bigger and better drugs to give those 50% of patients who don’t respond to Herceptin.

When I ask the question, why is the medical community still using IHC & FISH, the response is: that’s all there was available since we began treating with Herceptin, it’s all these docs know from their time at medical school; also, the pathology/laboratory/hospital community makes money from the interpretation of IHC/FISH results so there’s a reluctance to cutoff that revenue-stream; and for the most part, Herceptin seems to work; finally, for those patients for whom Herceptin doesn’t work, there’s another drug on the market called XYZ.

For those that are firmly aboard the OncoRevolution train, you’ll remember that the other drug available to HER2-positive tumors is a drug that crosses the blood-brain-barrier, whereas Herceptin does not.

Brain metastasis occurs much more frequently for patients on Herceptin vs. patients not on Herceptin – but don’t confuse cause and effect here. Herceptin doesn’t cause brain metastasis, it simply does not cross the blood-brain-barrier and thus has no ability to mitigate tumor development within the central nervous system.

That other drug does cross the blood-brain-barrier. If I was a doc, I would want to know if my patient has a ton of HER2 expression, or relatively low levels. The max score of IHC is 3+, and IHC is looking directly at HER2 protein expression. FISH is looking at DNA, and it’s just a ratio of DNA, not HER2 expression.

Come on folks, someone has to be keeping up with all this. Let’s change the world. Check that, let’s improve the way our families and neighbors are being treated by oncologists, pathologists, and the entire pharmaceutical industry. IHC is even being used in ongoing clinical trials for colorectal cancer, nonsmall cell lung cancer, ovarian cancer, etc. I promise there are better solutions out there than IncrediblyunHolyCrap.

Is it time for me to research what the heck a hashtag is? Help make this info go viral, join the OncoRevolution.

The Greatest Story Never Told

For anyone who has been keeping tabs on the exciting recent discoveries from MD Anderson Cancer Center, Dr. Jim Allison, and the “Moon Shots Program”, you’ll know that there are significant links between oncology and immunology.

With that in mind, onto the next post…

Over the weekend I have been researching both Monogram Biosciences and the HERmark assay; here’s what I discovered:

A company called Virologic was founded by a group of scientists from the immunology & molecular virology division of Genentech, the exact same company that now markets the drug called Herceptin (keep calm, my fellow conspiracy theorists, this appears to be just a coincidence since Genentech is a world leader in oncology therapeutics). Interestingly, one of the original Virologic founders also formerly worked at the National Cancer Institute.

Virologic was established in 1995 to tackle the the most complex and pressing issue of the time, which in fact was HIV. Over the past 15-20 years Virologic’ HIV technologies have become the gold standard for personalized medicine in this field of HIV molecular diagnostics.

Every Big Pharma HIV clinical trial uses Virlogic’s technology to bring a drug to market, because Virologic has the most sophistic & reliable technology available to the HIV-treating community. Everyone knows it. Everyone uses it.

In 2004 Virlogic merged with a company called Aclara Biosciences for $75M, combining an existing virology/immunology biotech laboratory with a promising oncology biotech company. As a result of the merger, the new company became known as Monogram Biosciences.

More info can be found here:

http://www.advfn.com/news_ViroLogic-and-ACLARA-BioSciences-Announce-Merger_7801001.html

However, Aclara’s oncology platform, known at the time as “eTag” was not a finished product. Additionally, remember that the primary focus of this merged company was not necessarily oncology, it was HIV molecular diagnostics since that was where the revenue stream was coming from. To that end, Monogram launched a novel technology for the management of HIV, what is known as a companion diagnostic, in 2008.

Consider for a moment how much resources, time, and effort the Monogram scientists must have devoted to bring this new assay to market in 2008; now remember that the Aclara merger occurred in the summer of 2004. The point is, the very first publication that Monogram was able to put forth on their oncology platform was not until the very end of 2008, one that was published in early 2009.

Now, who here remembers the economic crisis of 2008 & 2009? Everyone was affected in some way, and Monogram was no exception. Monogram was hemorrhaging money back then and was unable to raise any cash from financial partners, and the management team was forced to sell the company. Monogram was acquired by Laboratory Corporation of America (LabCorp) in June of 2009 for $106M plus Monogram’s $50M in debt.

Virologic’s $75M merger with Aclara now appears to have been a costly mistake.

The point of all this history is that HERmark – the first commercially available technology to come from Aclara Biosciences’ eTag platform – did not hit the market until 2009 since HERmark still needed to undergo significant tweaks & enhancements.

The eTag technology that was acquired from Aclara was transformed by a group of brilliant scientists into what is now known as VeraTag technology. However, these immuno-oncology wizards were forced to focus on HIV diagnostics in a desperate attempt to launch revenue-generating technologies in an established HIV market – to both save a sinking company and to provide some breathing room to focus on the oncology franchise.

HERmark was thus launched in the US in 2009 during one of the most severe economic recessions in recent times, one that forced Monogram to sell all it’s intellectual property to LabCorp for a song later that same year. This is not meant to condescend LabCorp, they clearly have some savvy accountants and visionaries leading mergers & acquisitions.

LabCorp did not stop with the acquisition of Monogram, however; they acquired Genzyme Genetics in 2010 for nearly $1 billion dollars. Genzyme Genetics was a megalith in genetics, oncology, and personalized medicine; this was a coup for LabCorp.

However, note that the highly sophisticated technology that Monogram had just launched a few months prior, HERmark, was now falling to the bottom of the priority list among Genzyme’s portfolio of oncology diagnostics. HERmark is a complex assay that was being positioned to replace technologies that had been used by oncologists and pathologists since these dinosaurs were in medical school; talk about an uphill battle.

Between 2010 & 2013 Monogram’s scientists were busily launching multiple assays designed to assist physicians who treat both HIV and Hepatitis C, but all the while they also found time to publish a number of highly intriguing papers to oncology & pathology publications – papers documenting the power of HERmark.

Yet all these publications were falling on deaf ears because no one was having conversations with physicians about the clinical value of this new information to assess a woman’s HER2 status (whether or not the woman will benefit from a HER2 targeting agent, such as Herceptin). And clearly, no one was having conversations with the American Cancer Society because as of 2014 they still do not even reference HERmark among known HER2 diagnostics. The tragedy of all this is that Monogram’s VeraTag platform can also be used for nonsmall cell lung cancer, prostate cancer, ovarian cancer, melanoma and various other cancers that are defined by human epidermal growth factor receptors (HER).

Yet the entire oncology, pathology, and pharmaceutical communities are still using technologies developed in 1941 & 1980 to stratify patients for HER-targeted therapies – because no one has seemingly even heard of the HERmark assay, let alone VeraTag technology.

The bottom line is that at the intersection of biotechnology and business we discover which companies execute sounds strategies to improve both healthcare and patient’s lives, and which companies fall victim the the realities of capitalism.

Forget pink, I’m going to get mistaken for a Pinko as I lay the frameworks for an OncoRevolution.

 

Many crumbs make a cake

As I write that title, take note that sugars feed cancerous tumors. If anyone here knows someone who is affected by cancer, the first thing you need to do is be sure that person knows the direct correlation between sugar & cancer. There was a great publication put out recently in a magazine from Whole Foods called Well Being Journal, and the title on the cover was “Sugar and Cancer”. You can find the edition online, it’s from March/April 2014.

Anyways, I wanted to provide a very brief update on my mini-progress this week, to anyone still wanting to take part in this revolution. At times I grow weary, as I’m sure everyone does when faced with an uphill battle with seemingly insurmountable odds. But then I thought about this in the form of a mathematical analogy (I’ll keep it simple, don’t surf away just yet).

Everyone here remembers a sine wave, right? Now what about a 45 degree angle? Still with me? Well imagine a sine wave that is pointed slightly up and to the right, gently aiming for that perfect 45 degree angle.

That’s how I like to think of progress. It’s never a straight line up, we always go two steps forward, then take one quick step back – recharge our batteries – then another two steps forward. This weekend I definitely need to recharge my batteries.

However, I made some progress this week.

If anyone took the time to read that article from the link I posted in the last entry about 1984 and the ungood, one of the prominent thought leaders referenced from that link wrote me back the other day. He basically outlined the path forward, the challenges faced to get HERmark to the mainstream, and the establishment’s rationale for using the aforementioned outdated technologies.

It was a great email response, totally thorough and polite. Certainly encouraging, yet he also downplayed HERmark’s overall clinical significance due to a need for more clinical trial research data. Therein lies the problem though, as he also flat-out acknowledged that current trials are still using IHC & FISH.

I’ll chalk-up this interaction as a glimmer of light in a dark tunnel, one that quickly faded but whose memory still is imprinted on the back of my retinas (man that feels deep, let’s just say it gave me a bit of hope).

I also spoke with my former academic adviser who was very receptive to the cause and put me in touch with one of his colleagues who is involved in cancer research. That colleague, unfortunately, was not very helpful and didn’t have any contacts to provide me with. He actually was studying mechanical properties of circulating tumor cells in the bloodstream, and didn’t seem to take much of an interest in this cause.

However, persistent as I am, I decided to go the route of the MBA program at that same school, my alma mater, since I had some success with a contact I made at MIT’s Sloan Business School as I mentioned earlier. Apparently all MBA programs nowadays have a Healthcare Club, or students who are interested in pursuing careers in the healthcare industry. I was able to get an email contact, but will wait until after the weekend to send that communication. I’ve learned that if you ever want to bury information in someone’s inbox, you send it to them late in the afternoon on a Friday.

Let’s hope I can stumble upon some like-minded OncoRevolutionaries (as I send this late in the afternoon on a Friday…).

 

1941 = Ungood: Is it 1984 yet?

Before starting, I would like to ask for some help from my small audience: we need to turn this viral internet thing into a force for good. Those wacky videos of cats playing with water and dogs on skateboards were good for a laugh; I think we can all agree that it’s time to get serious, and what better cause than this.

For anyone here who hasn’t read George Orwell’s book 1984, please check it out from the library or download it from Amazon, it’s a thrilling book (from what I remember, it was ages ago that I was forced to read it in high school). If memory serves, the protagonist is living in a society where everyone is constantly being monitored by Big Brother, and where you aren’t allowed to say things like “bad” because it would show dissension; you had to use words like “ungood”.

Now don’t get me wrong, I’m not here to bash society or to make a political statement. I’m just here to expose some truths about the current state of breast cancer diagnostics, and in the process I hope to both change & improve the way women are being treated.

(Now onto the science…)

I’m also not here to outright bash ImmunoHistoChemistry, or IHC (if this is your first read don’t worry about it, you don’t need to know what it means, just play along and be angry with the rest of us for a minute). It was a great technology back in 1941, and it developed an essential application in the 1970’s by assessing the clinical picture of cancerous tumors. The point is, technology should evolve.

Every year I see NFL players wearing pink in October, and I see people running marathons to raise money for cancer research. Then there’s the “save the tatas” movement, and every corporation in the world has some type of pink logo or memorabilia.  When I learned that the diagnostic tool that is being used as the standard of care for all newly diagnosed breast cancer patients is IHC, I couldn’t believe it. Then when I learned that all the Big Pharma companies are still using IHC in their clinical trials to validate their drugs (on live patients, mind you – not guinea pigs), I got pist.

Where is all the money that’s being raised going???

So to simplify this story about IHC, think about Lab A that is an ethical business operating on 50 Main Street. Well, business is business and wouldn’t you know it that Lab B decides to open shop on 51 Main, right across the road. Totally fair in this capitalistic world we live in, I’ve seen 4 gas stations at a single intersection. Completely legit.

Both Lab A and Lab B perform the IHC assay. They have both hired a pathologist to interpret the results under a microscope. When the pathologist makes a call, an insurance plan gets billed for his/her service, and Lab A and/or Lab B gets reimbursed for that service. Totally fine and dandy, up until to this point I hope everyone is still with me.

Now let’s get back to the revolution bit:

Did you know that Lab A will only get the same result as Lab B 80% of the time when using IHC methodologies – for the same tumor sample from the same patient taken on the same day? Now get this: it’s actually common knowledge. The reproduceability of this IHC assay is only approximately 80%, and yet it is the standard of care for clinical trials for HER2-targeting agents (and HER3 targeting agents too, but that’s a story for a different day; think nonsmall cell lung cancer), as well as the standard of care at each and every oncology practice in the nation. Hold your horses, it goes even deeper.

An IHC result, as identified by this pathologist (hopefully he got good sleep that night), will report either 0, 1, 2 or 3. That simple. 3 means the patient can use the drug called Herceptin, which is considered a good thing, whereas 0 & 1 results mean the patient cannot use Herceptin. Not a terrible thing, just means a bit fewer options.

So what about if IHC results a 2? Well as you probably guessed, that means “equivocal”, or “we don’t know”. I can’t believe this is the technology we’re still using to this day as the standard of care, can you? Astonishing. And remember, this was all based on the subjective call of a pathologist, not state-of-the-art quantification assay using the latest innovations.

Now who here saw the news report from last week or the week before describing how much doctors were getting paid by Medicare? Connect the dots, my friends, connect the dots. Drug makers need to get their drugs approved, and labs need to stay in business. I’ll let you finish this tangent, I have to get back to breaking down why the technology developed in 1941 – yet is the standard of care in 2014 – is garbage to begin with.

Remember what a score of a 3 means? It meant the patient can be given a drug called Herceptin, which actively targets a tumor cell protein known colloquially as HER2. Everyone has google so I won’t go into what this means for now, but know that it is generally received as good news, in a world when a patient is seemingly only getting bad news, when IHC gives back a 3 result there is a sense of relief.

Please don’t shoot the messenger for what I’m about to tell you.

3 is the highest score on IHC, and that is the last stop for oncologists treating breast cancer in most clinics around the country. Put the patient on Herceptin and let’s all hope for the best. Herceptin only works approximately 50% of the time, folks. There, I said it.

I’m going to repeat that: Herceptin, the drug that was identified as beneficial for patients to use according to a technology developed in 1941, only works in roughly 50 out of every 100 cases. How can that be so? The technology was so accurate wasn’t it? Or could it be that the pathologist who read it made a mistake? He/She’s a professional, he/she couldn’t have.

He/She possibly didn’t, actually. But mistakes are made in the actual processing of the sample, before the pathologist even gets a chance to make a subjective call. IHC is flawed. Everyone knows it. Everyone still uses it. The ASCO/CAP guidelines still say it can and should be used. That, my Older Readers, is what the kids nowadays are calling “kray-kray” (ie, crazy. I’m sure at least one of you was glad that I translated).

This post is getting a bit long so I’m going to leave you with a last piece of fury, but you have to promise to bring some more friends in here to get the low-down on what’s being done to our family members across the country – due to sheer negligence.

Herceptin is a large molecule that doesn’t penetrate the brain, or more technically the central nervous system, otherwise known as the blood-brain-barrier. There is plenty of documentation describing how patients taking Herceptin develop brain cancer, because Herceptin doesn’t cross the blood-brain barrier.

Hold onto your socks folks: there are other drugs out there on the market today that do in fact cross the blood-brain-barrier, and work just as well as Herceptin, but are only approved AFTER a patient has failed to respond to Herceptin – which is approximately 50% of the cases. I couldn’t believe it either (I’m assuming I’m making myself clear, and that I have a few readers who know someone who knows someone who was once had breast cancer).

The savior technology that I described in previous posts, known as HERmark (yet apparently not know to the American Cancer Society), has shown that at extremely high HER2 expression levels, patients have a higher propensity to develop brain metastasis (cancer spreads to the brain more readily). With that info in hand, I as a physician, would probably not give Herceptin to my patient should I see a HERmark result with a very high quantitative number of HER2 protein expression, since Herceptin doesn’t cross the blood-brain-barrier, and I don’t want my patient to develop a brain tumor as well. I would look for a different drug that actually does cross the blood-brain-barrier. This isn’t a marketing campaign for drug companies so just ask Dr. Google for the name of that drug.

It’s mind boggling to think that our lives are being dictated by physicians who learn their trade in big teaching institutions that get a ton of funds to research clinical trials from mega pharmaceutical companies – then only to go out into private practice and continue the same thing they were taught, using outdated technologies and thereby using ineffective drugs.

Is anyone following all this? I could really use some help; women could really use some help. Who’s going to help me light some well-positioned fires to light up the night sky, and expose the fraud of our medical diagnostic industry – starting with breast cancer diagnostics for HER2 screening.

Seriously folks, this is really, really ungood. I would love to go into further detail about the IHC results that produce a 0 or a 1, but it’s late and I’m a bit weary for the day. Just trust me when I say I’ll explain in more detail later that IHC is wrong at least 20% of the time, possibly up to 50% of the time – and many patients who are not being given HER2 targeting agents, which are potentially life-saving treatments, actually would have responded favorably.

A technology that is wrong 20% of the time, and is only reproduceable 80% of the time, and is interpreted subjectively by Dr. Joe Schmoe is no better than a coin flip. Garbage in, garbage out. No wonder Herceptin only works 50% of the time.

For those wanting further reading on this topic, head over to this site (it may take a minute to load). And trust me, I have already reached out to every single person referenced in this article:

Click to access bth05_3p023.pdf

Who’s willing to make the OncoRevolution go viral?