Drug to prevent blood clots

Considering how many BC patients actually die of blood clots, this new drug is very interesting:

http://www.bloomberg.com/news/2012-12-08/blood-thinner-from-pfizer-bristol-myers-blocks-leg-clots.html

What cost in 2 months delay in diagnosing/treating Advanced Breast Cancer?

This paper gives us some idea:

Waiting ≥ 60 days to initiate treatment was associated with a significant 66% and 85% increased risk of overall and breast cancer–related death, respectively, among late-stage patients

http://jco.ascopubs.org/content/early/2012/11/16/JCO.2012.39.7695.abstract

PD-991 with Femara

CDK inhibitor along with femara giving 26months PFS instead of <10 months PFS with femara alone.   Phase II trial only.   But still impressive.

http://www.fool.com/investing/businesswire/2012/12/05/pfizer-presents-phase-2-data-showing-investigation.aspx

http://erc.endocrinology-journals.org/content/18/4/C19.long

TEDMED 20 greatest medical challenges

There's one item that includes Cancer as "Management of Chronic Conditions".   I don't think majority of stage 4 aggressive breast cancer is really manageable yet, certainly not chronic in the way diabetes and heart disease patients have decades to expect.

Here's the list:

www.tedmed.com/greatchallenges

Don't get me wrong, I love TED, and would probably love TEDMED too.  But apparently cancer cure is NOT very challenging for them.   

Komen acknowledges stage IVers, great start!

the girl in the komen ads and why she personally support komen:
http://mybiggirlpants.blogspot.com/2012/02/i-stand-with-susan-g-komen-for-cure.html

i also agree with the great commentary by Ginny Knackmuhs:
http://mbcnbuzz.wordpress.com/2012/09/10/stage-iv-ad-from-komen-is-this-a-crack-in-the-pink-wall/

quote:

Call me crazy, but maybe some day we’ll actually see a Komen ad that says this:

“The true source of HOPE for metastatic disease is research. That’s why we at Komen are dramatically increasing funding for research into the cause of metastases (the spread of cancer) to stop it in its tracks and save the lives of the estimated 155,000 women and men living with metastatic or stage IV breast cancer in the US, as well as the lives of 30% of early stage survivors who will have metastatic recurrences in the future.”

NBCC progress report

http://www.huffingtonpost.com/fran-visco/breast-cancer-awareness_b_1772341.html

http://www.breastcancerdeadline2020.org/2020/2012-progress-report.html

http://www.breastcancerdeadline2020.org/assets/pdfs/breast-cancer-deadline-2020.pdf

Pink Coverage is skewed away from metastatic breast cancer

Quote:
The National Breast Cancer Coalition says there are many "myths and misunderstandings" surrounding breast cancer and that the public has been misled into thinking scientists are close to finding a cure. That’s due in part to media coverage, which does not always “reflect the realities of the disease,” the group’s report says.
...
For instance, in an analysis of coverage during National Breast Cancer Awareness Month in October 2011, the report says, many stories focused on young women’s personal triumphs and effective treatments. “The majority of personal accounts were primary, early stage, breast-cancer diagnoses. Often times, a picture was painted of survivors who are disease-free and overcame the disease,” the report says. “Only about 1 in 9 articles portrayed women battling metastatic disease.”

http://www.thedailybeast.com/articles/2012/08/13/the-media-s-pink-ribbon-problem-coverage-is-skewed-study-says.html

NBCC is running a fund raising campaign till 8/31 with 2-1 matching from Joyce Goodman Fund:
http://www.breastcancerdeadline2020.org/homepage.html

Genome associated with tamoxifen resistance

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286962/

Plus a paper on NF1 breast cancer:
http://www.genetics.org/content/early/2012/07/20/genetics.112.142802.long


Another link to a talk by Dr Topol of Scripps Institute about the barrier to whole genome sequencing.   Signing up is free of charge.   Please check out the comments:
http://boards.medscape.com/forums?128@@.2a342d7d!comment=1

Orphan Drug Designation

Does MBC qualify?

http://www.forbes.com/fdc/welcome_mjx.shtml

A Detective Mystery

http://www.cbsnews.com/8301-504763_162-57498490-10391704/how-scientists-stopped-superbug-that-killed-6-by-using-dna-to-track-its-source/

Pubmed: A Love Letter

Dear Pubmed,
I love you so much.   The "Results by year" bar graph on the right is really really cool.   When I make any queries, you always check how many papers you got.   If you have enough data, you will make a bar graph to show me how many papers on published in the most recent decades.   This way, I get a quick gauge on the research interests of thousands of breast cancer researchers, and how they wax and wane.

http://www.ncbi.nlm.nih.gov/pubmed?term=Insulin%20breast%20cancer
http://www.ncbi.nlm.nih.gov/pubmed?term=triple%20negative%20breast%20cancer

For example, someone tells me to take DIM for breast cancer.   So I asked you:
http://www.ncbi.nlm.nih.gov/pubmed?term=DIM%20breast%20cancer

You said: "83 papers total" over the years, 3-4 from 2012, many are talking about other things than DIM.
I said: OK.  I will pass.

Then I asked you:  should I consider metformin for breast cancer?
http://www.ncbi.nlm.nih.gov/pubmed?term=metformin%20breast%20cancer
You said: "160 papers total", with 20+ papers from 2012 alone.
So I figure that metformin must be interesting.

Then I asked you:  some patients swore by "oligometastatic breast cancer" and clobbered me for suggesting maybe it's rather uncommon:
http://www.ncbi.nlm.nih.gov/pubmed?term=oligometastatic%20breast%20cancer
You said 32 papers over the years, none from 2012
So I say, hmmm.   This doesn't seem a very active field, maybe it reflect the difficulty of clinical trials in this area, maybe it reflects the rarity of this subtype.    

Then I asked:  is HGF an interesting area for understanding?
http://www.ncbi.nlm.nih.gov/pubmed?term=HGF%20breast%20cancer

Guess what pubmed says?   Anyway, I suspect that one day you will save my life.    I just wish clinicaltrial.gov is as cool as you.

2007 Overview of Therapy Resistance from MD Anderson

Check out the tables.   Very informative.    Include response rate statistics for various common 1st line 2nd line 3rd line breast cancer therapies, and mechanisms of therapy resistance.   

http://www.ncbi.nlm.nih.gov/books/NBK6306/

Japanese Engineer: The last Ninja

http://news.yahoo.com/63-old-engineer-japans-last-ninja-053736959.html

Quote:
Many of their traditions were passed on by word of mouth, so we don't know what was altered in the process."

And those skills that have arrived in the 21st century in their entirety are sometimes difficult to verify.

"We can't try out murder or poisons. Even if we can follow the instructions to make a poison, we can't try it out," he said.

So clinical trials for BC cure is difficult?   Try refining the art of ninjutzu!

More quotes:

Kawakami first encountered the secretive world of ninjas at the age of just six, but has only vague memories of first meeting his master, Masazo Ishida, a man who dressed as a Buddhist monk.

"I kept practising without knowing what I was actually doing. It was much later that I realised I was practising ninjutsu."

Haha.   I first encountered BC maybe 10 years ago, and I kept practicing BCutzu without knowing what I was actually doing...

Who wants to be the last breast cancer patient?

In Memory of StitchyPhish

My cancerversary is coming up.   Since the beginning of my BC journey, I have witnessed the passing of maybe 100+ women.   Dear to me with their generous sharing of their lives and courage, and giving me a peek of the terrible devastation of metastatic breast cancer.

StitchyPhish on BCO died a couple of days after my diagnosis and was the first I remembered.  I still read her blog:
http://meganpinkblog.blogspot.com/2011/09/megan-lally-1091980-09012011.html

I'll always remember her.

C Diff: Overuse of antibiotics

http://www.usatoday.com/news/health/story/2012-08-16/deadly-bacteria-hospital-infections/57079514/1

CoolBreeze on BCO is also a wealth of information on this particular hazard.   I learned about this from her blog for the 1st time.

http://www.butdoctorihatepink.com/

Also, fecal transplant is gaining acceptance as a 1st line treatment for C diff, before it used to be 2nd/3rd line treatment because of the ick factor.  Even autologous transplant is possible if you are going to have antibiotics use.   Personally, I'd add fecal transplant into my bucket list...

A bunch of nurses are commenting on c-diff stool smell.   "Rancid meat",
"sweet funky smell".   

http://allnurses.com/general-nursing-discussion/characteristic-c-diff-32623-page3.html

I also looked up on internet for C-diff diarrhea pictures.     

Poem: State of the Art Cancer

Funny poem by Carol Miele:

bcmets.org/articles/153243

State of the Art Cancer

by Carol Miele

I have ‘state of the art' cancer,
For every question there's an answer.

Individualized chemotherapy? We got it!
Targeted therapy? No prob...we got it!

Want it given through a port?
Or injected in your butt?

We can give your chemo with a pill,
‘Oh....my heart be still!'

Want to join an experimental trial?
Our goal is to go the extra mile!

Our Über modern infusion center has it all,
Your own TV, computer, and even a waterfall!

We guarantee our Oncology Team is first rate,
And their knowledge base and certs are up to date.

Our nurses are so compassionate & caring,
They'll comfort you when treatment's overbearing,

We are a comprehensive cancer center,
Offering ‘state of the art' care to all who enter.

Sleek MRI equipment and ultra cool scanners,
We hired the very best architects and planners.

Rapid turnaround time on results of tests,
And our radiation treatment's the very best.

But most of all, we offer care you can afford,
I was so impressed, I jumped onboard!

Wait! Just one more thing, I have a question,
They nod with uncurbed enthusiasm, no hesitation.

When will there be a cure for my cancer?
Oh! Sorry, for that we have no answer.

True Innovation Or Fake Innovation

http://opinionator.blogs.nytimes.com/2012/05/27/in-medicine-falling-for-fake-innovation/

 

I kind of agree that some innovations are impressive sounding but increase costs without bringing significant benefit.    BUT:   every breakthrough has humbler beginnings.   Davinci robots is NOT the end of robotic innovation in surgery or other healthcare field.   It's just one of the first application of a nonlinear technology that will one day transform the world.

 

Check out this video of a girl whose life is transformed by robotics, human machine interface and 3-D printing.   One day I may need this technology too:

http://www.pcworld.com/article/260439/a_3dprinted_exoskeleton_made_from_lego_plastic_changes_lives_for_children.html 

Nonlinearity

Recently the stage IV forum on BCO has been a sad place to visit with several active members and young members' passing.   Reality of cancer is not pink and pretty. When I feel the reality weighing on me, I remember 3 things:

1.   Cancer does not grow linearly.  It grows exponentially.   That sucks

2.   Guess another thing that grows nonlinearly?   Computer power and affordability.  

3.   Our knowledge does not grow linearly.   In the last 10 years, MBC death rate (5 year) has been dropping around 1% a year, which comes to about 30%-50% 5 year survival rate currently.  This is bad.   BUT, we must not extrapolate into the next 10 years that 5-year survival rate will be 40%-60%.   It could be better than that, may be worse than that.   We need to harness nonlinear progress in technologies to battle this nonlinear disease called cancer.

This is an article from NEJM, chronicling progress in cancer research.  We do not have a cure, but we will get there.  Sooner or later.   With clinical trials and support for fundamental research and urgency in reforming the process of clinical trials, we will be there sooner rather than later.

http://www.nejm.org/doi/full/10.1056/NEJMra1204479

Quote: "At its peak in the early 1980s, the NCI accounted for 23% of the budget of the NIH, yet it supported 53% of the research in molecular biology in the United States. And the results have been explosive"

Tests you can do at home: for diabetes and cardiovascular health

When I first started I have no idea these things are all available at home.   So I'm sharing these products as I discover them.   I'm like a kid in candy shop, very happy but I have not tried or calibrated any of them yet.   So read the reviews before you buy:

them:http://www.amazon.com/CardioChek-Starter-Cholesterol-capillaries-lancets/dp/B0042APAVS

Cholesterol checks 

http://www.amazon.com/A1cNow-Monitor-Plus-10-tests/dp/B001HX2V1K

A1c monitors 

http://www.amazon.com/Response-Parameter-Urinalysis-Reagent-Strips/dp/B001EUAXZM

Uralysis tests

http://www.amazon.com/STANBIO-STAT-SITE-Hemoglobin-Test-Cards/dp/B001DLS87W
Hemoglobin test

Someone on another thread is saying things like "it's not accurate", "overdiagnosis", "your conclusion is not sound", blah blah blah.   I'm like:  come on, I know you are a certified health care professional.   But, have some imagination.   Here is the future:
http://www.qualcommtricorderxprize.org/

more details in my blog http://killerboob.blogspot.com
Dx 8/29/2011, IDC, 2cm, Grade 3, 1/1 nodes, ER+/PR+, HER2-

Magic Bullet for Lung Cancer and its Drug Resistance Problem

http://cenblog.org/the-haystack/2012/06/asco12-data-digest-combating-resistance-in-lung-cancer/

Magic Bullet for Melanoma and How scientist overcome drug resistance

http://sciencefriday.com/segment/07/13/2012/tumors-evade-treatment-with-help-from-neighboring-cells.html

http://cenblog.org/the-haystack/2012/06/asco12-data-digest-overcoming-resistance-in-metastatic-melanoma/

Very good blog talking about the same story:

Not long ago, metastatic melanoma was considered a graveyard for clinical research. But last year brought a major breakthrough in treating skin cancer: the approval of Roche's Zelboraf (vemurafenib), a small molecule that has proven highly effective at treating the roughly 50% of the patient population that carry the BRAFV600E mutation.

However, Zelboraf has limitations. Patients' disease eventually becomes resistant to the drug and the lesions caused by the skin cancer tend to return after 6 to 9 months.

In the backstory, it's the full genome sequencing that has become cheaper to $4000 that will help development of both targetted drugs like anti-BRAF and understanding drug resistance further.   I think the Broad institute is a customer of Complete Genomics.   I have no financial interest btw.   

More quotes:

An amazing thing about current melanoma research is that several physician-scientists involved in the clinical trials are also actively involved in translational research-this is sadly the exception rather than the rule, in oncology. But the connection between basic science and bedside has meant new targets are being identified and quickly tested in the clinic. 

How they pulled off this trick on melanoma is what is important.   Cancer is smart, but people are smarter.

An impressive waterfall plot of tumor shrinkage for patients (n=77) with the BRAFV600K mutation drew gasps from the audience - only four patients failed to respond to the combination, while the majority had a response of 30% or better. This isn't something you see every day in cancer research! Unlike the short lived responses we have seen with single agent therapy, the median duration of response for the BRAF naive patients with the combination was 11.3 months. Treatment given for a median of 10.7 months and just over a third (38%) were still ongoing. With regards to efficacy, PFS was 7.4 months across all dose cohorts, which is slightly above what one might expect for single agent therapy at full dose. 
 ...
He highlighted several key mutations that are druggable – aside from BRAFV600E and K, there is also c-KIT, Q61NRAS, NRAS wt and BRAF wt, where wt stands for wild type. Inevitably, the survival rates for these subsets varies, with NRAS mutants having the worse prognosis.

Complete Genomics: Full Tumor Sequencing for $4000

http://www.reuters.com/article/2012/07/12/us-completegenomics-shares-idUSBRE86B0PQ20120712

http://www.completegenomics.com/public-data/cancer-data/

http://www.completegenomics.com/services/cancer/

http://www.completegenomics.com/news-events/press-releases/Complete-Genomics-Announces-New-Technology-Developed-to-Set-Standard-for-Clinical-Grade-Genomes-161946595.html

Quote:  

"The Nature paper by Peters et al. describes how our LFR technology uses ‘barcoded' DNA to generate whole genome sequencing with approximately one error in 10 million base pairs, or just 600 errors in an entire human genome," said Dr. Rade Drmanac, the company's chief scientific officer and inventor of the LFR technology. "This represents a 10-fold increase in accuracy for Complete and is unmatched by any high-sensitivity method currently available."

In addition, Complete's LFR technology provides, for the first time, accurate whole-genome sequencing from as few as 10 to 20 cells (only 100 picograms of DNA), making it an ideal choice for small sample clinical sequencing applications including circulating tumor cells, fine needle aspirations, and pre-implantation genetic diagnostics 

More quotes:Gene sequencing companies, which also include bigger names Illumina Inc and Life Technologies Corp, cater to a client base that mostly comprise educational and research institutions and compete on price.

The sector has recently come under pressure from a cut in the funding provided by the National Institutes of Health (NIH) for basic science research.

As the technology is yet to see widespread commercial adoption, the funding cut is one of the biggest issues faced by the sector that is on a persistent drive to bring down the price of gene sequencing to about $1,000.

Currently, the average price is $4,000-$5,000.

My take:  This price is affordable for some patients.  Comparible to the $2000 charged by Oncotype DX, and BRCA testing and others, generate a lot more information.  Its accuracy and how little sample it takes (CTC) is a big sell for me. 

Some types of BC has tumor mutations that are not standard BC, more like standard other cancer, which may have well targetted drugs for them.       It could perhaps help your onco find a better targetted 2nd/3rd/4th line chemo/biological and gave the patient valuable time with better tolerance.   It could give researchers more insight on why you are or are not responding to certain treatment or become resistant.   It could in future change the way clinical trials are run and lead to the cure.   Faster, more accurate, cheaper.  

So my Cato bit:  support research, support clinical trials to find the MBC cure.   Note the NIH funding cut, the public needs to invest more money into basic science, better technologies and finding the cure, and spend less money on expensive tests/procedures/drugs/charities that really don't deliver the bang for the buck.

http://www.forbes.com/sites/matthewherper/2012/07/13/can-complete-genomics-escape-the-valley-of-death/

Except they are having trouble convincing doctors to use them.   Here is where patients could come in.   Patients have the right and the duty to demand the newest and best and cheapest technologies, to encourage innovation and save money for themselves and for the health care system.   Illumina's 90% market share is not healthy for the development of this nascent market and notice how Illumina had to drop their price from $20000 to $4000 due to the new entrants into this market.    


Quote from wikipedia:

In June 2009, Illumina announced the launch of their own Personal Full Genome Sequencing Service at a depth of 30X for $48,000 per genome,[1] and a year later dropped the price to $19,500.[2] This is still too expensive for true commercialization but the price will most likely decrease substantially over the next few years as they realize economies of scale and given the competition with other companies such as Complete Genomics and Knome.[3][4] As of May 2011, Illumina reduced the price to $4,000.[5][6]

Not enough Patients in Clinical Trials, much less Combination Drug Trials

http://ecancer.org/tv/pubdate/1424

It's a great talk by Prof Thomas Tursz from EU.   I agree that the status quo in BC clinical trial is not acceptable.   Each semi-successful drug takes 15 years from bench to approval, 100s million dollars, not to mention the 9/10 failed drugs.    Combination drugs may well help, (Herceptin, Everolimus, Pertuzumab all succeed in combination treatment) but there is a big problem with mathematics.

Usually a good treatment (not a specutacularly good 70-100% response treatment, maybe a 30-50% response treatment) takes 500 patients in a randomized blinded controlled trial to get statistically significant proof that it actually is good, not just a statistical fluke, a placebo.   I explained this in another thread:  A clinical trial on 23 patients is like 23 coin tosses. After 23 coin tosses, say I get 15 heads vs 8 tails. I could say that this coin is weighted heads/tails ratio almost 2, that's very different from 1. But I am not very confident of this conclusion because the sample size is too small. Now if I toss 500 times, and still gets heads/tail ratio of 2, then I become very confident of this ratio.

That's why randomized double blinded clinical trial with 500+ patients is still the gold standard in clinical trial. That's expensive and requires lengthy recruiting. When you consider that different subtypes of BC (TNBC, claudin-low, normal-like, basal) may have only 2%-10% patient population, you realize how tough it would be to find 500 patients with this small subtype to test a drug specifically targeting this type. Add to that cancers evolve to become drug resistant, it become even tougher. 

Now, let's move on to the even more difficult tasks of testing combination treatment.  Suppose we have 3 drugs (A,B,C) that has cleared phase II trial with good results, each requires 500 patients to go through phase III trial for approval, that's 1500 patients required total.   Now if we want to explore combination treatment, then there are at least 4 combos, AB, AC, BC, ABC.   That would require 7*500=3500 patients for a full test.

Suppose we have 4 drugs (A, B, C, D), there will be 15 combos+singles to fully test, requiring 15*500=7500 patients.   Suppose we have 5 drugs, we will need 31*500 patients.   So on and on.

It's exponential, doubling with every new promising drug to test and we do not have this many patients.     But "In clinical trials, 97% of patients in Europe are not in a trial", I think numbers are similar in US.   That is a HUGE problem.

Traditional clinical trials especially on early stagers require long time commitment (like 5 years) from patients. So traditionally late stagers are the main force of clinical trials.  Late stagers are fewer in numbers (50000/year), the ones with the right subtype of BC rarer (say 5000/year for TNBC, which has more subtypes), the ones with good performance statuses are fewer still (say 2000/year), the ones with good performance statuses living near a research facility are rarer yet (say 1000/year), the ones with good performance status who are willing to serve in clinical trials are still fewer(I don't know how many, but certainly less than 50% from my observation), and so it's hard to recruit enough of them to test new drugs, much less combinations. End result is: traditional clinical trial process takes 15 years and 1 billion dollars for any good drug to make through.

This is why I'm so excited by ispy-2.org. Newly dxed early stagers needs to commit only months to either control or experimental arm. Basically a couple of dose to see if it (standard chemo or standard+new drugs) works, if not, they change chemo or go ahead to surgery. The new drugs are generally the most promising drug that has already been tested for safety. 200k/year newly dxed patients with good performance status could potentially be recruited which means quick recruitment. A new drug if demonstrating efficacy, could go from bench to approval in as little as 5 years. Even FDA is excited.

If Henry Ford is on Titanic, he would not say: let's do a handmade lifeboat for everyone. He'd make an assembly line that churns out lifeboats. Ispy2 is the kind of assembly line for new cancer drugs that he'd be proud of.

ispy-2 has potential to increase patient participation dramatically by reducing patient commitment.   That said it only could test certain type of drugs.   In general, we need much greater patient participation across the board, and we need a different clinical trial model with different end-point (phase I, II, III may need to be changed),  we need to invest in better animal model/preclinical model, better blood/imaging tests for progression, different end-point.   We will get the MBC cure, but the PROCESS for developing cure urgently needs to be improved. 

Mars Panorama

http://www.wired.com/images_blogs/wiredscience/2012/07/mars-rover-opportunity-panorama-fifth-winter-nasa-asu.jpg


What's the connection of cancer with Mars Panorama?  I know but I won't say it.

AIDS and breast cancer

Anti-HIV drug may work against TNBC.  Currently it's in mouse only.   But we need to find the bull's eye on triple negative cancer cells, so that new drugs can target these basal (=TN) beasties.

http://www.sciencedaily.com/releases/2012/06/120606155712.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Ftop_news%2Ftop_health+%28ScienceDaily%3A+Top+News+--+Top+Health%29

Since these drugs are already available for HIV patients, they may get to human clinical trials  sooner and the whole process can be easier.   

Another interesting article on AIDS and Breast cancer risk

"Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection"

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014349

It appears very few patients have both AIDS and breast cancer, yet, for some reason.

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702011000400016&lng=en&nrm=iso&tlng=en

The impact of HAART on the HIV epidemic includes greater life expectancy, a decreased risk of AIDS-defining cancers, and an increased risk of some non-AIDS-defining cancers.3,21,22 Breast cancer incidence has not been shown to be higher among HIV-infected individuals.21,22 Among women, a pattern of decreasing risk of breast cancer has been shown with increasing time since AIDS diagnosis.23 Among men and women, a statistically significant decrease in the incidence of breast cancer has been observed following the AIDS epidemic in Tanzania.24 In France, the incidence of breast cancer was significantly lower in HIV-infected women than in the French general population7,8 This apparent deficit in breast cancer cases may be explained by underreporting or competing mortality. In the United States, the deficit of breast cancer cases among women followed in the Women's Interagency HIV Study is explained by an overall lower frequency of established risk factors.25,26 

MMTV virus in breast cancer

http://jnci.oxfordjournals.org/content/101/5/293.full.pdf

 Unfortunately, even if there is a cure based on this interesting findings, it will take 15 years to go through clinical trials and 1 billion dollars.   In the meanwhile, it needs to compete with 100s of promising drugs (which turn out to be duds) for patients, researchers and dollars.   It's possible it may lose in the early competition for lack of tweaking, lack of patients, lack of money and languish forever.

That's why I keep trumpeting the virtues of ispy-2 trial, and other new clinical trial designs.    Cancer evolve drug resistance fast,  cancer drugs development is too slow in the last 30 years.  

Cancer drug development is sadly lagging the AIDS drug development.  AIDS bursted unto the scene in 1980s, killing its patients within 1 year.   The urgency of AIDS epidemic translated to 10% of NIH funding and massive researching effort and within 10 years, science worked out many of the previous unknowns and there were multiple drugs that target HIV.   Now AIDS patients could look forward to a normal life expectancy.   AIDS was the greatest challenge and the greatest triumph of modern medicine.

Metastatic breast cancer or lung cancer is not there yet.

For Independence Day post, this is the lyrics for Neil Diamond's Coming to America.  It could be easily about any form of human affliction, be it poverty, tyranny, AIDS, MBC or Metastatic Cancer for general.   Cancer is smart, so we need to keep trying keep dreaming keep investing:

Far, We've been traveling far, Without a home, But not 
without a star
Free, Only want to be free. We huddle close Hang on to a 
dream
On the boats and on the planes, They're coming to 
America. Never looking back again, They're coming to America.
Home, don't it seem so far away Oh, we're traveling light today In the eye of the storm, In the eye of the storm
Home, to a new and a shiny place. Make our bed, and we'll say our grace, Freedom's light burning warm, Freedom's light burning warm.
Everywhere around the world They're coming to America. Every time that flag's unfurled They're coming to America
[. From: http://www.elyrics.net/read/n/neil-diamond-lyrics/america-lyrics.html .]
Got a dream to take them there; They're coming to 
America. Got a dream they've come to share, They're coming to America
They're coming to America
They're coming to America
They're coming to America
They're coming to America
Today, today, today, today, today
My country 'tis of thee, Today, Sweet land of liberty, Today, Of thee I sing, Today, Of thee I sing -- Today

A Ship Called Titanic

If i'm on a ship called Titanic, I'd be busy reading up on "Sailor's guide to icebergs" or "Surviving shipwreck for dummys".    I'd be running around calling out to everyone to get on improvising a lifeboat or thermal suit or start to acclimate to cold water.    I would be the oddest character in the movie.  I will not be enjoying life to the fullest, whatever that means.   And until that Titanic docks safely, I'll just delay my partying a bit.

Imagine Kate telling Jack in cold water: "Jack you need to have a positive attitude".    Well I keep getting that from well meaning people.  

Failing lungs? No problem

Here's your oxygen shot straight to your blood stream:

http://www.popularmechanics.com/science/health/breakthroughs/no-lungs-required-injected-oxygen-
to-keep-patients-alive-10087551

A lot of kinks to work out, also a bridge solution that solves 10 minutes in crisis situation.   But cool idea nonetheless.  

Deserve to Die

Think it's for lung cancer.   It's an interesting campaign

http://digg.com/newsbar/topnews/deserve_to_die_posters_pop_up_in_some_u_s_cities

Human Microbiome Project

NYT comes out with a couple of gems related with the bacterial ecosystem inside us.

 

http://www.nytimes.com/2012/06/14/health/human-microbiome-project-decodes-our-100-trillion-good-bacteria.html?pagewanted=all 

This kind of study was impossible/very expensive to do just a few years ago.   But now it produces wealth of information.     First on healthy people and healthy bacterias.   Some day for cancer patients and bacterias.   I wonder if there's difference.

 

http://www.nytimes.com/2012/06/19/science/studies-of-human-microbiome-yield-new-insights.html?pagewanted=all

 

Imagine the researchers presenting their poop-transplant results with a straight face   And their beaming parents and their proud offsprings.   ROFL.

Let me jump aboard my hobby horse again.   Support research, support clinical trials and donate your *samples*.

A long thread on BCO about this and canine oncologist:

http://community.breastcancer.org/forum/73/topic/789218

Interesting TED talk about multilingual bacteria

http://www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html

and another TED talk about an immortal cancer that is passed from one animal to another.

http://www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html

 

Finally, clinical series live with some very interesting talks:

http://www.clinicalserieslive.com/login

Neoadjuvant clinical trials and anti-metastasis clinical trials

New anti-metastasis trial design, alternative better cheaper cures:

http://www.cancer.gov/ncicancerbulletin/061212/page4

New neoadjuvant clinical trial design for early stager newly diagnosed patients, faster cheaper clinical trial for the cure, sooner rather than later:

http://ispy2.org/

FDA and scientists are doing their job, trying to find the cure sooner and cheaper.   They need patients to learn about these new trial designs and spread the word. Every women should hear about it, especially high risk women before diagnosis, and newly diagnosed. Neoadjuvant = pre-operative. anti-metastasis would help everybody, including current stage IV.

Tumor Tissue Donation

I looked around in clinical trials for keywords like "genome", "microRNA", "tumor tissue", "tissue bank", "cell line", "dna", and of course "breast cancer".   You could also look for "NCI".   In looking for trials, look for NCI sponsored trial if possible. And ask for data sharing among researchers.

http://clinicaltrials.gov/ct2/show/NCT00032201?term=breast+cancer+tissue+banks&rank=18

This one is creating cell lines from high risk breast tissue. if you had breast cancer before, your noncancer breast tissue might be immortalized! "To establish a repository (facility in which tissue samples can be preserved and stored for many years) of cell lines from high-risk breast tissue to allow researchers to learn more about changes in breast cells that may cause them to develop into breast cancer."

http://clinicaltrials.gov/ct2/show/NCT00899301?term=tumor+tissue+breast+cancer+DNA&rank=16

http://clinicaltrials.gov/ct2/show/NCT00899509?term=tumor+tissue+breast+cancer+DNA&rank=10

http://clinicaltrials.gov/ct2/show/NCT01000883?term=tumor+tissue+breast+cancer+DNA&rank=15

http://clinicaltrials.gov/ct2/show/NCT01334021?term=genome+breast+cancer&rank=4

http://clinicaltrials.gov/ct2/show/NCT00897702?term=genome+breast+cancer&rank=16

http://clinicaltrials.gov/ct2/results?flds=Xh&flds=a&flds=b&flds=c&flds=g&flds=j&term=breast+cancer+microRNA&show_flds=Y

http://clinicaltrials.gov/ct2/results?flds=Xh&flds=a&flds=b&flds=c&flds=g&flds=j&term=breast+cancer+tissue+banks&show_flds=Y

Prediabetes + Breast Cancer

I just found out I'm prediabetic with impaired insulin resistance.

Here are the things I found out:

About 20% of people 20 years and older are prediabetic.  

http://diabetes.niddk.nih.gov/dm/pubs/statistics/#Pre-diabetes 

Prediabetic patients get BC at about 3 times the rate of normal population

http://www.cancernetwork.com/conference-reports/asco2011/content/article/10165/1874808 

http://www.usatoday.com/yourlife/health/medical/cancer/2011-01-22-breast-cancer-diabetes_N.htm 

Prediabetic patients should be treated with metformin and get on low starch diet/exercise.   So check your blood sugar to make sure you are not prediabetic.

http://tristarpub.com/endo2011/?p=90

Friday Laugh

This story is supposed to be somewhere near Afghanistan:

young woman:   Auuugh, I heard my chance of dying in child birth is 5% per delivery.   

woman's mom says:  That's cruel!   Who did such a cruel study!  All women are individual with individual risks!

young woman:  1% or 5%.  I still don't wanna die!

woman's mom: My dear, look at this as a glass half-full situation, 95% chance you'll be ok!   Life is beautiful and pink.   The sunshine so nice.   Look at every day as a blessing...   In my mother's day, the chance of death was 10% per delivery.    Wait, let me be positive, in my mother's day, the chance of life was 90%!

young woman:  I need to do something about it.    try to improve the hospital conditions for example or join a clinical trial!

woman's mom:  I'm so sad.   You have a beautiful future that's 95% sunshine, why do you persist in dwelling on the negative.

[It goes on on and on]

Stem Cell Conference in Japan

EU is debating cutting Embryonic Stem Cell funding.   Leading scientists asked for continued funding:

http://www.forbes.com/sites/johnfarrell/2012/06/15/stem-cells-in-the-news-and-yokohama/

Science/medicine is accumulative.    All the therapies we took granted today were built on top of sweats and blood and suffering of people and animals.   We have a debt to repay and an investment to make.

Also a FDA regulation viewpoints by forbes:
http://www.forbes.com/sites/gerganakoleva/2012/02/19/stem-cells-fda-and-the-edge-of-science-three-expert-viewpoints/

Recurrence rate and stage IV survival rate: UK Study

Depression Alert!!!!   Don't read it if you don't like ugly, cruel, barbaric stats.   It's about a sneaky, ugly, cruel, barbaric disease called metastatic breast cancer:
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*   Don't keep reading, if you can't handle ugly, cruel, barbaric stats:
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http://www.guardian.co.uk/society/2012/jun/12/breast-cancer-recurrence-study-macmillan?newsfeed=true

Notice for early stagers diagnosed around 2000, 10 year recurrence rate is 20+%.  AND the worse than recurrence rate: the life expectancy of the recurred patients: they survived for an average of 17.9 months after being diagnosed for a second time.

Breast cancer has no cure/survivors, ladies, sorry to pop your pinkwashed bubble.    The chemos you are on are mostly 20,30 years old.    The hormone therapies you are on are 10-30 years old as well.   Herceptin is 10+ years old.   Newer drugs extend life by months, not even years, let alone decades.

Prevention is an expensive deadend that took 30 years to get to this.   Support metavivor or metastatic breast cancer research and join clinical trials.   Try earmark your donation to go straight to scientists/graduate students or specific research. 

Whacky Idea 2: Oncolytic Virus

In news yesterday, oncolytic virus (reovirus) hitch a ride to kill cancer cells:
http://www.medicalnewstoday.com/articles/246619.php

Keypoints:

a.  they found virus replicating factory inside the tumor

b.  they didn't find the virus replicating factory in normal tissue.

c.  the virus evaded immune system 

Because virus can be engineered to add a little gene to create a potent cancer toxin, so reovirus become a perfect delivery system.

But c. is also scary.  and b. is important for the safety of patient. 

----------------   Whacky idea alert -------------------------------------

What if we re-engineer a mastitis virus, something that home into breast cancer cells to replicate inside a breast cancer cell? 

http://www.slideshare.net/Oncos/cgtg102-oncolytic-virus-in-breast-cancer-iir-conference-may-5-2010-3964027

Other gene therapy platform:
http://www.mdanderson.org/newsroom/news-releases/2011/gene-therapy-kills-breast-cancer-stem-cells-boosts-chemotherapy.html

Whacky Idea I: Thank you Berlin Patient

So the Berlin Patient, the 1 patient in the world who was cured of AIDS, got me thinking.  

What if, we find some highly effective breast cancer resistant gene, which could be an immunity gene X (Metabric study already identified some, should be more by other researchers).   Then we find a patient with both BC (preferably MBC) and leukemia, call her P.   Because P needs bone marrow transplant anyway, we gave her a donor's bone marrow who happened to have breast cancer resistance gene X.  

This idea is similar to cancer vaccine, just a little more far fetched.  

AIDS has a cure. Where is the MBC cure?

A man Brown with AIDS developed unrelated leukemia. 

http://nymag.com/health/features/aids-cure-2011-6/

http://news.yahoo.com/study-digs-secrets-keeping-hiv-check-180404115.html

Quote:

Only about one in 200 or 300 HIV patients is able to naturally keep the virus from developing into AIDS without the help of medications. 

...

 After chemo, the leukemia came back. Brown's last chance was a stem-cell transplant from a bone-marrow donor. Hütter had an idea. He knew little about HIV, but he remembered that people with a certain natural genetic mutation are very resistant to the virus. The mutation, called delta 32, disables CCR5, a receptor on the surface of immune-system cells that, in the vast majority of cases, is HIV's path inside. People with copies from both parents are almost completely protected from getting HIV, and they are relatively common in northern Europe-among Germans, the rate is about one in a hundred. Hütter resolved to see if he could use a stem-cell donor with the delta-32 ­mutation to cure not just Brown's leukemia but also his HIV.

Hütter found 232 donors worldwide who were matches for Brown. If probabilities held, two would have double delta 32. Hütter persuaded the people at the registry to test the donors for the ­mutation; his laboratory paid, at a cost of about $40 per sample. They worked through the list. Donor 61 was a hit.

Notice how tentative the man's leukemia doctor was. He did not know that much about HIV but made a connection and a leap of imagination, went through a lot of extra nonstandard procedure to get his patient the perfect donor.    The patient, Brown, with the help of transplantation, is now "cured" of HIV.    Brown doesn't even need to take antiviral cocktails that already gives HIV patients near normal life expectancy.    

The story is compelling.   Please take a moment to read through them.

What does it mean for breast cancer patients?   Note how AIDS, even without cure, has life expectancy of 63 year old, while MBC patients has life expectancy of a few years/months from diagnosis.    Yet, some MBC patients with certain immunity genes have the best prognosis for BC.   One day these genes can be figured out and maybe a cure.   For this day to be soon, patients and doctors and researchers need to work together.

More quotes from nymag:

---------------------- 

For Brown's cure to be relevant on a wide scale, it would have to be possible to create the delta 32 mutation without a donor and without a transplant-preferably in the form of a single injection. As it happens, progress toward that goal has already begun, in the laboratory of Paula Cannon at the University of Southern California. Instead of a donor, Cannon is using a new form of gene editing known as zinc finger nucleases, developed by the California company Sangamo BioSciences. Zinc finger nucleases are synthetic proteins that act as genetic scissors. They can target and snip a specific part of the genetic blueprint: They can, for instance, cut out the code that produces the CCR5 receptor, yielding a cell with HIV resistance.

---  End quote 

Genetic therapy is a direction that needs to be pursued for MBC.   The same article also mentioned a HIV charity on a used-car sized budget trying to drum up enthusiasm for the HIV cure, how the idea of cure was met with great skeptism and self-doubt even by Hutter, and how this case of cured AIDS patient (by an obscure doctor who knew little about AIDS) for years received little notice from the AIDS scientific cycle or the broad public, .

I think this story has great deal of relevance for the search for MBC cure, and is a great inspiration for patients/activitists/doctors/researchers alike. 

All newborn babies are ugly

Early stage cancer cures are ugly for a long time.   Pertuzumab failed as a single agent cure, succeeded in multi-agent therapy.   Everolimus failed as a single agent breast cancer drug, succeeded in multi-agent therapy.  Herceptin was almost cut by Genentech before clinical trials.  The list goes on and on.


Now here's another ugly one:

http://www.cancertodaymag.org/Spring2012/Pages/blocking-metastatic-disease.aspx?Page=1

"Despite Psap's promising start, however, Watnick cautions that the first clinical trials of any such drug in people are at least two years away. It's also possible that his passionate investment could turn out to be a false start: Researchers have found thousands of molecules connected in some way to the spread of cancer. Most of these molecules never turn into plausible targets for cancer treatment-though a select few continue to advance slowly toward becoming potential new therapies. " 

But the idea is an interesting one:  can you stop metastatic cancer by something made by nonmetastatic cancer?   The PI is looking for investors.      

Folate-Receptor Alpha: Drug target

A new folate-receptor alpha vaccine is going to clinical trial at Mayo:
http://clinicaltrials.gov/ct2/show/NCT01606241?term=mayo+folate+breast+cancer+vaccine&rank=1


This is the paper I found by the PI:
http://jco.ascopubs.org/content/24/26/4254.full.pdf


It goes into the peptide vaccine's composition and the folate receptor target is also expressed in small mounts in kidneys.   So people with autoimmune problems or kidney problems may need to be careful (excluded in the clinical trial).    


Overall vaccines tend to have low toxicities so hope this trial would recruit easily. 


Another strategy that can target folate-receptor alpha is similar to TDM-1's conjugate strategy:
http://www.springerlink.com/content/yv05130861863525/ 


A lot of work needs to go into how to shuttle the chemo through the receptor-binding into the cancer cells, and unload the chemo once inside.    

I'm also reading a book "Emperor of illness",   it told of the story of Herceptin.   If not for the dedication and risk-taking of a small band of scientists/advocates/patients, Herceptin would not have been invented, or its adoption would have been signficantly delayed.    

 

In fact, in every major development in cancer cure chronicled in this book, personal passion and risk taking played a significant role.   So when I see early projects like this, I ask myself, what can I do to help?   As a patient, the least I can do is

1.  I can educate myself on different clinical trials and participate in relevant clinical trials.   Donate my patient record/tumor samples to researchers

2.  Instead of buying a fancy wig or eat something unhealthy, I can donate to a metastatic breast cancer fund or directly to researcher that's working on something earlystage but interesting.    My vanity/sweet tooth budget can go to research :-)

3.  I can share information with other patients