Why scans are good.

Brain surgeon buried his proposal ring in the sand...  Then he lost it...
After hours of searching (with volunteer help), he called a ring detector service.   Metal detector shows up and find the ring in no time:
http://news.yahoo.com/blogs/lookout/marriage-proposal-goes-awry-brain-surgeon-loses-ring-164800976.html

This is why we need scans, and CT/US assisted surgeries.   And the girl said yes.

Massive Parallel Gene Study on ER+ tumors

I live in interesting times.    Massive Parallel Gene Study on ER+ tumors:

http://abstract.asco.org/AbstView_114_95183.html


NK immune cells genetic profiling predicting early/late relapse on early breast cancer
http://abstract.asco.org/AbstView_114_99068.html

Cabozantinib

Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2.

 

results:

abstract.asco.org/AbstView_114...

recruiting phase II trials

clinicaltrials.gov/ct2/results...

From Wiki:

Positive data from clinical trials indicate cabozantinib is particularly beneficial in metastatic advanced prostate cancer. 97% of patients either had stabilization or improvement in bone malignancies. The median time to disease progression was 29 weeks. 

 

Wow.   Breast cancer trials have not gotten as good a result, but not far behind.

 

Autoimmune culprit, anti-cancer ally?

Th17 cells, implicated in autoimmune disease, also our potential ally in fighting cancer

http://www.newscientist.com/article/dn18075-autoimmune-disease-cells-harnessed-to-fight-cancer.html

Note how recently Th17 was discovered (2005)!    Note also how the very learned scientist from MD Anderson got a result that surprised them.  This paper is 2009.  There are also a lot of literature that seem to implicate Th17 in cancer.

It will take at least 10 years for any drugs to come out of this.   But I'm awed by how much we don't know and remain to be learned about human body.   My eldest (5) claims he already knows everything.   I want to be there to pop his bubble when he's 13 and still thinks he knows everything!

More recent article reviewing the role of Th17:
http://carcin.oxfordjournals.org/content/32/5/643.full

It's like a murder mystery with a cast of 1000 and hidden characters dropping in all the time.

Snortle, the best medicine

A clinical trial anyone?

http://nomorefriends.net/

http://www.inspire.com/groups/advanced-breast-cancer/discussion/laughter-the-best-medicine-1/

Survey for Long term survivors

5+ years with mets.   Especially people with liver/brain/lung mets and triple negative.   Newly diagnosed patients really need inspiration and information.   Thank you!

https://docs.google.com/spreadsheet/viewform?formkey=dGw2MVJsN0FPM3BYNkYtWUtkZFRNUWc6MQ

Self-regulation

A long term survivor on bcmets.org pointed me to this German paper which goes into Iscador in detail.   I am not convinced that Iscador is effective in prolonging life.   But there is a surprise hidden in table 4.  Their data suggests that patients with certain psychosomatic traits (self-regulation) enjoys prolonged survival (several years vs 1 year for control group).
http://www.iscador.com/Content/ContentTrakker/Articles/1cf0ade6-8722-4693-ac81-20306f0baa35/3_32.pdf

So I went to look up the 16-question questionaire they used to determine "self-regulation" score.   Stephanie pointed me to this 106 questionaire instead:
https://secure.localweb.com/attitudefactor/SRItest.html

I tried taking the test but the software has some kind of error that won't take my submitted form.   The questionaire seems to be measuring independence, assertiveness, life-purpose, resourcefulness in taking care of self.   I'm almost certain that Kathy Rich and Carol Silverander (the 2 long term survivers) probably got "self-regulation" in spades...

Their stories are reviewed here:
http://killerboob.blogspot.com/2012/05/carol-silverander-long-term-survivors.html


So congratulations to all the patients who exercise 45 minutes/day through bone pain/nausea, minimize their stresses, and control their urges to reach for cookie/cheese/red meat jars.  You may well live longer because of your persistence and forbearance.


However, I'm going to not be so positive in the following paragraph.   So if you wants to be positive all the time, you need not keep reading here:






several years are better than several months.  But not enough.    The goal is the cure, that MBC patients live decades to the normal life span, not years, not months, not days.   It is beyond cruel to condemn a young mom with metastatic breast cancer to several months, or years for that matter, just because she has sweet tooth, has nicotine habit, has no time to exercise or a stressful life.

Till there is a cure, every breast cancer patient is a stage IV.  

Carol Silverander long term survivor's story

Lately I've been reading Carol Silverander's "With the Help of Our Friends from France"
http://www.amazon.com/With-Help-Our-Friends-France/dp/0976831619/ref=sr_1_1?ie=UTF8&qid=1337619327&sr=8-1

A little about Mrs Silverander.   She was dxed with hormone positive early stage breast cancer and underwent chemotherapy and radiotherapy and lumpectomy around 1997 in her early fifties.  Two years later, she started to suffer from nausea and went to have checked up for suspected hepatitis, but learned she has metastasis to liver instead.    Thus began her 8 year journey with extensive innumerable liver mets, some about 2cmish.   She also mentioned bone metastasis.   During her treatment, she had xeloda (other chemotherapies), hormone treatments + herbal treatment (from a doctor in France, hence the title of her book).   Both worked to stabilize her cancer, though as far as I can tell, she never achieved NED.

Here are the things that I feel might be a factor in her survival:
1.  Mrs Silverander has a persistence that is remarkable and admirable (I conclude this because any person who writes a book after stage IV diagnosis is probably more persistent than me).   Since her stage IV diagnosis, she made a number of life style changes:
a)   She started 45 minutes/day treadmill exercise regimen + yoga.   Given her persistent streak, I have no doubt she maintained this regimen
b)  She has been vegetarian before, but turned to chicken/fish to supplement her protein
c)  on advice of her french alternative doctor, she reduced her intake of dairy, which has been her staple previously.   She also cut out/reduced sweets and soy intake.
d)  She managed to reduce stress, on advice from her French doctor

2.   Mrs Silverander travels extensively internationally.   Why I consider this a factor in her survival, please refer to my previous posts.
3.   Mrs Silverander takes a number of herbal therapies, including Iscador, all prescribed by her French alternative doctor.   These prescriptions were listed at the end of her book.
4.   Her cancer is hormone positive, probably Her2-, either luminal A or luminal B.   Either way, tumor marker tests accurately reflected her cancer's progress.   In that way, she gained a survival advantage because doctors (conventional and alternative) can better gauge her tumor's response and she herself can gauge the impact of her lifestyle changes.  Another survivor, Ms Rich from my earlier posts also share this advantage.
5.   Mrs Silverander also suffered from subclinical hypothyroidism concurrently with her breast cancer, till it was corrected with the help of her French alternative doctor.   Hypothyroidism in women are often caused by autoimmune disease.    It was not clear whether she had tests which would have diagnosed her as autoimmune.

Please refer back to my earlier post about "Red Devil" by Katherine Russel Rich, another long term survivor of stage IV breast cancer.   I see a lot of similarities between the two women.   They seem to have both ER+PR+ cancers, responded to megace (though both hated them), both dropped tamoxifen very early on for side effects.   Some may be trivial others may not be.

http://killerboob.blogspot.com/2012/04/kathy-richs-red-devil-book.htm

Anti-malaria drugs being tested against breast cancer

some cancers seem to concentrate iron.

This is similar to malaria parasite. So there's some clinical trials that is trying malaria drugs on cancer. These drugs tend to have good safety profile. They are in cancer trials based on epidemiological and pre-clinical efficacy.

http://clinicaltrials.gov/ct2/results?term=Hydroxychloroquine+breast+cancer&show_flds=Y

http://clinicaltrials.gov/ct2/show/NCT00764036?term=artemisinin+breast+cancer
http://clinicaltrials.gov/ct2/results?term=chloroquine+breast+cancer

Phase I clinical trials: New paradym

Many patients won't consider phase I trial to start with.    With trials of more targetted medicine, this may change.

Quoted:

"Wheler is currently lead investigator for a trial at MD Anderson (similar to Bolero-2, which was a Phase III trial for advanced breast cancer patients) that has enrolled over 100 cancer patients to test Anistrozole (Arimadex®), an anti-hormone therapy agent, in combination with Everolimus (Afinitor®), a therapy targeted to cellular growth. In this particular study, if a patient develops resistance to either of the two drugs, then the strategy is to add a third drug to try and overcome the resistance. This means that treatment in this Phase I trial is truly tailored to both a patient's tumor biology and her response to therapy."

Pam Munster, MD
"Many patients will never consider a Phase I trial because they believe the drug being tested will be in such an early stage of its development that they will not benefit from taking it," says Pam Munster, MD, Director, Early Phase Clinical Trials Unit and Leader, Developmental Therapeutics Program, at the UCSF Helen Diller Family Comprehensive Cancer Center. "But we really try to make every effort to select the right drugs for patients, so they at least have a chance of a good response."

http://breastcancertrials.wordpress.com/2012/05/16/phase-i-clinical-trials-a-changing-paradigm/

Also a personal story about a stage IV patient, Susanne Hebert, 7 years survivor of stage IV.   Finally on a phase I clinical trial that gave her respite, Everolimus.   The rest is history.
http://breastcancertrials.wordpress.com/2012/05/16/personal-stories-suzanne-hebert/

The world is connected

The world is connected.   When I was a teen, if someone told me that I would one day:
a.  benefit from billions of dollars of the AIDS research.
b.  wish I have AIDS instead of another more deadly disease (say, breast cancer)

I'd not have believed it.   But here I am, 20 years later, both happened.    Breast cancer patients benefit from AIDS research because of all the knowledge we gained about the immune system, and how to treat immune compromised patients.   I do wish I have AIDS rather than breast cancer, because AIDS patients are closer to a cure than patients with metastatic breast cancer.

This new upenn study proposes, "daclizumab, already used for kidney transplantation, would be effective in depleting regulatory T cells (Tregs) and restoring the immune system's ability to fight tumors": ,
http://www.uphs.upenn.edu/news/News_Releases/2012/05/fda/

Linking back to another study of failed immune system:
http://killerboob.blogspot.com/2012/05/thin-red-line-around-breast-cancer.html

The plot is thickening!   A link to the small early stage clinical trial:
http://clinicaltrials.gov/ct2/show/NCT00573495?term=daclizumab+breast+cancer&rank=1

What a holy grail cure might look like?

7/8 complete response. This drug will definitely be fast tracked for this indication.  Yes it's a great development! No it's not for breast cancer, though a small percentage of breast cancer may ultimately benefit (inflammatory breast cancer folks should look for clinical trials).
 http://www.fiercepharma.com/story/pfizers-targeted-drug-knocks-out-child-cancers-small-study/2012-05-17 

 I'm not saying we should snub our noses at the drugs that is yielding 5%, 25% or 50% complete responses. the 5% complete response may well be harbinger of a targeted therapy that can be 90% complete response for a small subset of the very diverse breast cancers. Every small step is cause for celebration and many paths to the cure need to be explored. But this is what "cure" should look like. Targeted and effective. Till we have this kind of treatment for 99% of metastatic breast cancers, no one is a survivor.

Primary Prevention? Where is the cure?

I read 2 bios of women with advanced breast cancers, beating the odds with one living 20 years after stage IV dx, the other living 8 years after liver mets.   In both, their doctor at one point or other encouraged them with variations of "hang around, in a few years there might be cure".

Sadly both of them passed away without seeing the cure.    I just went through the same chemos/therapies they went through,.   For certain subset of stage IV BC patients (triple negative, luminal B), life expectancy has not significantly increased in 30 years. Many of these patients are young with younger children.   One of them on mother's day board quoted her 9 year old daughter saying "thanks mom for not dying".   Then there are story of Kate Greene, died of triple negative breast cancer, doctor gave her 18 months life expectancy, she got 18 days.

http://www.thesun.co.uk/sol/homepage/woman/4163841/Mums-List-Cancer-victims-moving-list-of-rules-for-her-sons-is-a-book-sensation.html

18 months prognosis, 18 days survival, these are the tragic reality of metastatic breast cancer.     So I understand stageIVer's frustration.    30 years, millions died, hundreds of billions of dollars spent, what have we got for a cure?   Just all those unnecessary mammograms that silently failed to detect most aggressive cancers in younger denser breasts?  "Primary prevention", is at best an interesting sidetrack, at worst is an expensive distraction.

In the same 30 years, AIDS has gone from a mystery 1-year death sentence, to become a chronic disease where patients can expect to survive near the normal life span.     That is not a cure, but close enough that every metastatic breast cancer patient would gladly swap her disease for AIDS.    There have been progress for MBC, but not enough.    Research dollars for MBC are small percentages of overall breast cancer fund raises, and there are so many exciting new directions that are not been explored at full speed.

Truth is, all breast cancer patients are stage IV.   The interest of every breast cancer patients are the same as the interest of metastatic patients, which is to find the cure.   It's important that early stage breast cancer patients not to be complacent of their "survivorship", but align their interest with the metastatic patients in support.

Why metastasis research is important for stage IV

http://www.nashuatelegraph.com/opinionperspectives/960655-263/bill-would-identify-scientific-advances-for-breast.html

I am not a fan of screening/prevention methods (mammograms, awareness, elimination  of  environmental causes that definitely leads to 2% of breast cancers, etc), as they have inherent limitations that will fail a big percentage of early stage patients and do no good at all for late stage patients.

However, research into metastasis and preventing metastasis is still a great direction because even late stage patients would benefit if further metastasis after NED could be prevented.

The cure has to come from a multi-pronged attack, understanding metastasis and preventing metastasis is an integral part.   Look at the cure for AIDS, ultimately it comes from a cocktail of drugs that does different things.   

If lawmakers really want to speed up the process for the cure, here are my suggestions:

1.  mandate or encourage clinical trials for patients of all stages.  and mandate better quality clinical trials that track patients long term, do genetic analysis of tumor samples, better target drugs and share raw data (while protect patient privacy).

2.  fund basic science and technological innovations, whether in high throughput DNA sequencing, wet lab or tissue regeneration

3.  make new targetted drugs cheap/fast to develop/try out.   Cooperate internationally.


Still I don't like "prevention of metastasis" as the "primary" focus.  It might be journalist speak for "let's get all the other patients on the bus and throw the current stage IV patients under the bus"...

Cancer stem cells

Note:  Cancer stem cells are not your normal stem cells.
Quote: " It is essential to appreciate that the field of solid tumor CSC research remains at a nascent stage compared with the leukemia stem cell (LSC) field, and, therefore, our understanding of solid tumor CSCs and their significance is a work in progress. "


Relatively old review from 2 years ago:

http://clincancerres.aacrjournals.org/content/16/12/3113.long

Understanding fundamental biology is fundamental to the cure for solid cancers.

Breast Cancer Vaccines

This article mentions some breast cancer vaccine and other cancer vaccine breakthroughs:
http://www.firstpost.com/living/breakthrough-in-immunotherapy-could-cure-cancer-300846.html

The newer vaccine testings tend to target earlier stages, unfortunately.  The later stages of breast cancer might also benefit from a multi-pronged attack like the AIDS cocktails.   A lot more work is needed.

I found its coverage of business aspect of vaccine development particularly interesting.   Especially in light of some recent postings on whether Neuvax will be a hit or dud:
http://www.thestreet.com/story/11507036/1/galenas-breast-cancer-vaccine-doomed-to-fail.html?cm_ven=GOOGLEN

http://seekingalpha.com/article/525841-mark-ahn-interview-neuvax-demonstrated-preclinical-and-clinical-benefit-in-all-levels-of-her2-expression?source=feed

Well, only clinical trials would tell.

Thin red line around breast cancer

How immune system fails to stop breast cancer.   Great images and insight.   These are the studies that need funding:

http://www.ucsf.edu/news/2012/05/11966/thin-red-line-around-breast-cancer

Pushing Stem Cells More

I have been accused of "pushing stem cells".   Here's why I think stem cell therapy can improve metastatic breast cancer patients' chances. 

1.  Heart stem cells help low LVEF-heart to regain muscle.   Implication to cancer patients?   If this research pans out, then patients who had already had lifetime doxocirubin or reaction to Herceptin can have more doxuribin/Herceptin if it's needed. 

http://www.mdanderson.org/newsroom/news-releases/2010/adult-stem-cells-help-injured-hearts.html

2,   Liver stem cell to reduce mortality after hepatic resection

http://www.ncbi.nlm.nih.gov/pubmed/22156926

3.   Liver stem cells to grow whole organ

http://www.wakehealth.edu/News-Releases/2010/Researchers_Engineer_Miniature_Human_Livers_in_the_Lab.htm

Prevention and screening is a deadend that yields decreasing marginal returns.  Innovation has always saved our butts, and will save our butts in future. I am happy to push for it and run commercials for it.    There are lots of things patients can do to accelerate the process, like participating in clinical trials, go to major NCI cancer centers, donating tissue and blood samples, ask questions to make sure the research data will be shared, push for better quality clinical trials to be designed.    My blog makes more elaborate cases for these patients participation.  Please don't be put off by the lousy English.   I am not an english major or a marketer, never will be.

Stem cell for liver regeneration

Liver regenerates naturally.   People can surgically remove 1/2 of liver and still be ok.  However, Breast cancer has the nasty habit of dispersing itself like dandalions across liver.   Some people who has big liver or total liver involvement will face high mortality risks if you cut more than 2/3 of liver.   And cancer patients are not eligible for liver transplant anyway.
Enter stem cell technology to allow entire organs to regenerate.  It's preclinical.   But it will be coming:
http://www.wakehealth.edu/News-Releases/2010/Researchers_Engineer_Miniature_Human_Livers_in_the_Lab.htm
Even if that is not an option, one can potentially inject stem cells into liver to speed up the regeneration process and reduce mortality risk and hence expand the usage of hepatic resection for metastatic breast cancer patients.
These technologies are improving from all over the world.  China/Germany/Japan are places to watch.    But be careful to sign up with any clinic who claims they already know how to do it.   Whatever they know and can do, should be reproducable by other labs/hospitals across the world.
Nobody knows for sure, that's why we need clinical trials, we need international effort for data sharing and trustworthy data.   Patients need to demand newer techniques and fund basic/translational research.

What can a Patient do?

I think patients can do a lot more than donating money.
1.  We can advocate for ourselves, demand genomic sequencing on our tumor samples (not oncotype DX which gives me 4 pieces of information), but something that will return gigabytes of your tumor DNA sequence so it can be analyzed in future in light of new research
2.  We can donate our patient record and our blood samples and our spare tumor samples to researchers who are interested (and who will share, that's important).   The 10 subcategory of BC was done based 2000 such patients.
3.  We can fund more old clinical trials to be retrospectively analyzed for DNA.   A lot of drugs failed on phase III at 5-20% clinical response.   These drugs may work 100% for some people with specific subtype of breast cancer.
4.  We can join clinical trials whenever we can.     Pediatric cancer made a lot more progress in the last 20 years because all kids with cancer join clinical trials.    Medicine advances fastest through clinical trials.   Just say no to the snake-oil salesman who wants to sell you the secret to survival; if it is a secret, if it's not reproducable, if it's not sharable, then it's likely worthless.
5.  We can fund fundamental biological research, in immunology, in brain, in stem cells.   One day, vaccine and stem cells will revolutionalize treatment of metastatic breast cancer.