http://www.forbes.com/sites/tommeyer/2013/12/16/hope-for-breast-cancer-patients-is-around-the-corner/

CDX-011 results are pretty good for triple negative MBC patients.   But still not good enough.

iSpy-2 shows 2 drugs winners

Quote:

Both drugs were tested in an unconventional mid-stage trial called I-Spy 2. The trial involves patients with cancers confined to the breast, where a cure is possible but the disease is at high risk of spreading to other parts of the body. In one of the novel features of the study, the drugs were measured on their ability to eradicate the cancer in just six months, before any surgery to remove tumors.

Veliparib, for instance, when combined with the drug carboplatin and a six-month regimen of standard chemotherapy, achieved a complete response in 52% of patients compared with 26% for patients treated with standard chemo alone, according to results presented Friday at the annual San Antonio Breast Cancer Symposium.

Typically, late-stage cancer drug studies succeed only 30% to 40% of the time, said Laura Esserman, director of the breast care center at University of California San Francisco and co-leader of I-Spy 2. Such trials can involve several thousand patients--many of whom wind up taking drugs that don't help them--and can take nearly a decade to get an answer.

...

Whether the promising results will translate into a speedier approval--or any approval at all--isn't assured. A key to the I-Spy strategy is that the FDA accepts a complete response at six months--meaning that no residual cancer cells can be detected after the tumor and lymph nodes are removed--as a surrogate for a long-term benefit. The aim is for FDA to allow a drug on the market on that basis, on the condition that follow-up research demonstrates a long-term benefit.

http://online.wsj.com/article/BT-CO-20131213-705589.html?dsk=y

Surgeon's skill at the Surgery table a Key factor of Success

Obvious, but apparently it takes 3000 year of medicine to state:

http://well.blogs.nytimes.com/2013/10/31/a-vital-measure-your-surgeons-skill/

News updates

What's new in metastatic breast cancer research

http://www.slideshare.net/DanaFarber/mbc-2013-talk-3-whats-new-in-metastatic-research-and-clinical-trials-mg-edited

AIDS Drug may work against cancer:
http://www.reuters.com/article/2013/10/25/us-cancer-hiv-idUSBRE99O0R920131025

More Satisfied Patients Die Sooner?

http://www.forbes.com/sites/kaifalkenberg/2013/01/02/why-rating-your-doctor-is-bad-for-your-health/

Also by Forbes, super computer Watson working on matching patients to clinical trials at MD Anderson
http://www.forbes.com/sites/bruceupbin/2013/10/18/ibms-watson-now-tackles-clinical-trials-at-md-anderson-cancer-center/

Tiny Pacemaker

Massive innovation in computer/cell phone/battery technologies enables this tiny pacemaker.
http://www.bbc.co.uk/news/technology-24535624

Within a decade, it could be even smaller with better battery life.   Innovation never stops.  It never stopped before and will not stop in the future.   Without even knowing a lot what we know today about immune system, HIV got a cure within 15 years of the virus being first discovered.

Are we the cancer patients, including the breast cancer patients the only ones stuck in an innovation-deficient hell, where the word "cure" dare not appear in peer reviewed scientific journals?   There are lots of hope, lots of interesting research, but the focus on metastasis is not always there.  Hopefully this is changing:
http://wrbw.membercenter.worldnow.com/story/23667473/fifteen-leading-charities-and-advocacy-groups-join-forces-to-change-the-way-metastatic-breast-cancer-is-understood-and-to-increase-focus-on-research



http://www.ncbi.nlm.nih.gov/pubmed/22956040
http://www.eurekalert.org/pub_releases/2013-10/gcrc-dav101513.php

Valproic acid encourages virus to fight cancer.   Dandy


http://www.aacr.org/home/public--media/aacr-press-releases.aspx?d=3179

OMI helps identify therapy response easily.

BXQ-350 for pancreatic cancer and brain cancer

This is about BXQ-350 for pancreatic cancer and brain cancer:

http://news.cincinnati.com/apps/pbcs.dll/article?AID=/201310130522/NEWS10/310130052&nclick_check=1

Quote from:

Getting this far has been an achievement of its own for Bexion’s team. Fewer than 10 percent of drugs that undergo animal testing ever make it to phase 1 human trials.

And its challenges are just beginning. About 10 percent of drugs that get this far ultimately gain U.S. Food and Drug Administration approval, a total that drops to 4.7 percent for cancer drugs, according to a 2011 study.

Triple-negative tumors targetted with cystine transporter blocker

http://www.eurekalert.org/pub_releases/2013-10/uoc--tbc100213.php

Timmerman found that she could significantly slow growth of triple-negative tumors using an FDA-approved anti-inflammatory drug called sulfasalazine to block a specific cystine transporter called xCT. While sulfasalazine itself would not be appropriate for treating cancer, Timmerman said, it could serve as a "lead compound" that could be used to develop drugs that specifically target xCT on tumor cells.

mouse model of Patient's MBC shows interesting similarity

http://www.sciencenewsline.com/summary/2013091923340031.html


This article goes over current TNBC treatment.   It offer hopes without the reality check that the so called "double"ed PFS probably means a few additional months.    Complete pathological response as experienced by this patient featured remains a "miracle", not the expected.
http://www.curetoday.com/index.cfm/fuseaction/article.show/id/2/article_id/2157

Perjeta approved Neoadjuvant use

http://www.onclive.com/web-exclusives/In-Historic-Vote-on-Pertuzumab-ODAC-Suggests-Approval-of-First-Neoadjuvant-Regimen-for-Cancer

Despite my reservation for adjuvant drug research, neoadjuvant regimen is a different thing and much more exciting development to watch, and has the potential to revolutionalize and speed up cancer research.


http://www.cancernetwork.com/conference-reports/asco2013/breast-cancer-symposium/content/article/10165/2157691

How a neoadjuvant studies shows that biomarkers changed during the course of early breast cancer therapy.


http://www.inspire.com/groups/advanced-breast-cancer/discussion/long-interesting-clinical-trials/

Someone on inspire posted a lot of interesting clinical trials collated list.

Entinostat breakthrough status

http://www.onclive.com/web-exclusives/Breakthrough-Designation-Granted-to-Entinostat-for-Advanced-Breast-Cancer

Quote:
In a March 2012 follow-up analysis published in the Journal of Clinical Oncology, the median PFS was 4.3 months versus 2.3 months, for entinostat and placebo, respectively (HR = 0.73; P = 0.06). In patients resistant to NSAIs (n = 45), the median PFS was 3.72 months compared to 1.78 months, in favor of the combination (HR = 0.47). - 

The median overall survival in the combination arm was 28.1 months compared to 19.8 months in the exemestane arm (HR = 0.59; P = 0.036). In a subset of patients (n = 49) with increased protein acetylation, the median PFS with the combination was 8.5 months compared with 2.8 months for patients without acetylation (HR = 0.32). 


My comment: Results are not terribly impressive.  But if this could be comboed with other targetted drug then this could be good.   

The key is the test for "protein acetylation"  (49/130).   The other patients might not have benefitted at all.   While the patients with increased protein acetylation (49/130)  seem to benefit at a much higher rate.



In other news:   Breast Cancer Index (BCI) Gene fingerprint identifies subset of HR+ EBC women at risk for 5+yr recurrence.   Lancet Oncology:
http://www.newsday.com/news/health/researchers-focus-on-likelihood-of-breast-cancer-recurrence-1.6056863

RealTime imaging of brain tumor using SRS

http://www.medicaldaily.com/new-laser-based-scalpel-may-revolutionize-brain-cancer-surgery-255492

Interesting article of metastatic cancer

http://www.onclive.com/publications/obtn/2013/August-2013/Developments-in-Metastatic-Cancer

NBCC deadline 2020

NBCC has a deadline 2020 project that seeks to end breast cancer by 2020.   They are currently fund raising with 2:1 matching, so you triple your gift match with donation until 9/30/2013.

I'm reading up on their progress report:
I like the fact that NBCC put a deadline date for BC.    This is unlike other charities that just splashes pink year after year till the founders live to a cushy retirement, and generations of women get marched through the adjuvant BC revenue generation therapy and get decimated by the MBC.

http://www.breastcancerdeadline2020.org/about-the-deadline/progress-reports/2012-progress-report.html

They fund a project called artemis that tries to end breast cancer by preventing metastatic breast cancer(MBC), it's another way of saying they are going to end breast cancer by researching adjuvant BC treatment.   They say don't expect silver bullet (for curing MBC).

But I want to see them going out on a leg and putting up a X-prize for actually curing MBC.   I want the silver bullet.   HIV patients got silver bullets, diabetic patients got silver bullets, malaria folks got the silver bullets, some leukemia folks got the silver bullets.   MBC and other cancer folks need to expect silver bullets and ask for the silver bullet (or the silver bullets) and not be distracted by any other shiny toys.

No more new mammograms, MRIs, PETs, and other half-baked detection/prevention mechanisms.
No more expensive drugs by extending MBC survival by 1 month, 3 month, etc.
No more adjuvant repackaging and remarketing of ok/great MBC drug that does not cure MBC and spend billions and 10 years to find out that this adjuvant strategy may not work.
No more quakery.

We have a real chance of getting the cure by 2020.   But let's make sure of it.

Miltefosine an anti-fungal/anti-protozoa drug may work on cutaneous BC

Old drug, response rate not that great (30%) not for too long either.   but interesting.

xtandi is also being tested for androgen positive TNBC.

Oncology Pipeline

Quoted below:

Table 1. Pipeline Agents with the Greatest Potential Impact in Oncology

Drug in Development	Manufacturer	Indications
Astuprotimut-r	GlaxoSmithKline	Melanoma, NSCLC
Ibrutinib	Pharmacyclics/ Johnson & Johnson	Chronic lymphocytic leukemia, mantle cell leukemia
Nivolumab	Bristol-Myers Squibb	Melanoma, NSCLC, renal cell carcinoma
Onartuzumab	Genentech/Roche	Gastric, NSCLC
Ramucirumab	Eli Lilly	Breast, colorectal, gastric, hepatoceullular carcinoma, NSCLC
Palbociclib	Pfizer	Breast
Rivantinib	ArQule/ Daiichi Sankyo	Hepatocellular carcinoma
Dabrafenib + Trametinib	GlaxoSmithKline	Melanoma

Attributes that were scored included mechanistic innovation, strength of prior published data, target indication population size, and level of competition. For more in-depth information on Kantar Health’s scoring methodology, please e-mail info@kantarhealth.com.

I'm also looking at GL-ONC1 and a few others.


http://www.onclive.com/publications/oncology-business-news/2013/june-2013/mining-the-pipeline-leading-investigational-products-and-areas-of-unmet-need/3

Table. Ongoing Phase III Immunotherapy Clinical Trials

Agent	Description	Tumor Type	Sponsor
AGS-003	Autologous dendritic cell	RCC	Argos Therapeutics
BioVaxID (BV301)	Autologous immunoglobulin idiotype	Follicular lymphoma	Biovest International
BV-NSCLC-001	Epithelial growth factor antigen	NSCLC	Bioven Europe
DCVax-L	Autologous dendritic cells	Glioblastoma multiforme	Northwest Biotherapeutics
GV1001	Telomerase peptide	NSCLC	Kael-GemVax Co, Ltd
HyperAcute-Pancreas (algenpantucel-L)	Alpha-gal-modified cancer cells	Pancreatic	NewLink Genetics Corporation
IMA901	Multipeptide	RCC	immatics Biotechnologies GmbH
Imprime PGG	β-glucan bound to neutrophils	Colorectal	Biothera
Lambrolizumab (MK-3475)	Anti-PD-1 monoclonal antibody	Melanoma	Merck
L-BLP25 (formerly Stimuvax)	MUC-1 peptide liposomal	NSCLC	Oncothyreon/Merck KgaA
Lucanix (belagenpumatucel-L)	Gene-modified TGF-β blocker	NSCLC	NovaRx Corporation
MAGE-A3 (astuprotimut)	Peptide-based	Melanoma; NSCLC	GlaxoSmithKline
Multikine (leukocyte interleukin)	Cytokine mixture	Oral cavity/soft palate	CEL-SCI Corporation
M-Vax	Autologous, hapten-modified	Melanoma	Avax Technologies
NeuVax (nelipepimut)	E75 peptide plus GM-CSF	Breast cancer	Galena Biopharma, Inc
Nivolumab (BMS-936558)	Anti-PD-1 monoclonal antibody	Melanoma; NSCLC; RCC	Bristol-Myers Squibb
POL-103A	Melanoma cell line antigens	Melanoma	Polynoma LLC
ProstAtak	Gene-mediated	Prostate	Advantagene, Inc
PROSTVAC	Poxviruses plus costimulatory molecules	Prostate	Bavarian Nordic
Rindopepimut (CDX-110)	EGFRv3-specific peptide conjugated to KLH	Glioblastoma	Celldex Therapeutics
Talimogene laherparepvec (T-VEC)	Genetically modified herpes oncolytic virus	Melanoma	Amgen
Vaxira (racotumomab)	Anti-idotypic monoclonal antibody	NSCLC	Recombio SL
Yervoya (ipilimumab)	Anti-CTLA-4 monoclonal antibody	Melanoma; NSCLC; prostate	Bristol-Myers Squibb

Sources
Cancer Research Institute, ClinicalTrials.gov, company websites

- See more at: http://www.onclive.com/publications/oncology-live/2013/july-2013/immunotherapy-hits-new-peak-asco-data-stir-excitement-investment/3#sthash.Qgdo77vY.dpuf

http://www.onclive.com/publications/oncology-live/2013/july-2013/immunotherapy-hits-new-peak-asco-data-stir-excitement-investment/3

TNBC may respond to blood cancer Multiple Myeloma Drug

Cancer cell has an interesting new paper, very early stages of course:

http://www.healthcanal.com/cancers/breast-cancer/41802-aggressive-triple-negative-breast-cancers-may-be-sensitive-to-drugs-that-clog-their-waste-disposal.html


Quote: 
By selectively turning genes off throughout the genomes of triple-negative tumor cells in vitro, Lieberman's team found that these cells absolutely require active proteasomes in order to live. When turned off, the cells die. 

These data suggest that triple-negative breast cancers may respond to treatment with drugs similar to bortezomib (Velcade®), a proteasome inhibitor that revolutionized the care of patients with the blood cancer multiple myeloma.

not exciting but interesting

http://www.sciencedaily.com/releases/2013/06/130605111527.htm

Lengthening drug response 30% sounds not too bad, except when you notice that you are still talking about a couple months more time, maybe.    15 years of MBC living is still the exception, not the rule by any form.


http://www.mountsinai.org/about-us/newsroom/press-releases/blocking-sugar-intake-may-reduce-cancer-risk-or-progression-in-obese-and-diabetic-people

Multitarget drug cocktail may be the way to go.   But the number of clinical trials that needs to go through is staggering.   

Quote: Armed with three new drug targets—glucose, the Ras/Src oncogenes, and Wingless/Wnt signaling—Dr. Cagan and his team identified compounds that can block the process. 

They treated the flies with acarbose, a treatment for diabetes; a compound called AD81; and a drug called pyrvinium. Acarbose blocked sugar conversion to glucose; AD81 cut off Ras/Src and caused cell death; and pyrvinium inhibited Wingless/Wnt signaling. Taken together, this cocktail of drugs substantially reduced tumor size and progression.

“Our study shows that sugar activates oncogenes in the tumor, which then promote insulin sensitivity, meaning that the exorbitant glucose levels in the blood pour into the tumor, having nowhere else to go in the insulin-resistant body,” said Dr. Cagan. “We have identified a three-drug combination that stops this signaling activity and tumor growth in its tracks, without affecting normal cell function.”

Neoadjuvant trial of Ganetespib shows promise for TNBC and HER2+ BC

Can not tell how durable is the response from the neoadjuvant study, but the response rate is phenomenal, especially when considering the abysmal record of TNBC treatmnet.
http://www.heraldonline.com/2013/07/29/5061751/synta-announces-enchant-1-breast.html


Ganetespib also shows good performance against some types of lung cancer:
http://medicalxpress.com/news/2012-01-ganetespib-kras-mutant-nsclc-monotherapy-combinations.html

It's possible that the cure for BC requires combo of several targetted therapies at the same time.

YADT for TNBC

http://www.a-star.edu.sg/Media/News/PressReleases/tabid/828/articleType/ArticleView/articleId/1855/Default.aspx

Yet Another Drug Target for TNBC: UBASH3B
Interesting, though the drug development would be 10 years later.


Some paper for mass scale stem cell generated liver cells:
http://www.liebertpub.com/global/pressrelease/human-stem-cell-derived-hepatocytes-regenerate-liver-function-and-extend-survival-in-mice-with-hepatic-failure/1287/ 

Human Stem Cell-Derived Hepatocytes Regenerate Liver Function and Extend Survival in Mice with Hepatic Failure

New Rochelle, NY, July 26, 2013 -- Researchers have generated functional hepatocytes from human stem cells, transplanted them into mice with acute liver injury, and shown the ability of these stem-cell derived human liver cells to function normally and increase survival of the treated animals. This promising advance in the development of cell-based therapies to treat liver failure resulting from injury or disease relied on the development of scalable, reproducible methods to produce stem cell-derived hepatocytes in bioreactors, as described in an article in Stem Cells and Development, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Stem Cells and Development website.

Massoud Vosough and coauthors demonstrate a large-scale, integrated manufacturing strategy for generating functional hepatocytes in a single suspension culture grown in a scalable stirred bioreactor. In the article "Generation of Functional Hepatocyte-Like Cells from Human Pluripotent Stem Cells in a Scalable Suspension Culture" the authors describe the method used for scale-up, differentiation of the pluripotent stem cells into liver cells, and characterization and purification of the hepatocytes based on their physiological properties and the expression of liver cell biomarkers.

David C. Hay, MRC Centre for Regenerative Medicine, University of Edinburgh, U.K., comments on the importance of Vosough et al.'s contribution to the scientific literature in his editorial in Stem Cells and Development entitled "Rapid and Scalable Human Stem Cell Differentiation: Now in 3D." The researchers"developed a system for mass manufacture of stem cell derived hepatocytes in numbers that would be useful for clinical application," creating possibilities for future "immune matched cell based therapies," says Hay. Such approaches could be used to correct mutated genes in stem cell populations prior to differentiation and transplantation, he adds.

Stem cell mutation and Marfan's disease/allergy

Stem cell mutation may confer metastasis risk:
http://www.obgynnews.com/news/top-news/single-article/stem-cell-mutations-in-breast-cancer-may-confer-metastatic-risk/a9fff020376e6e3bf3fe9667100905b6.html?tx_ttnews%5BsViewPointer%5D=1


In separate news, rare Marfan's syndrome shed light on a common affliction of allergy and asthma:
Losartan's effects on TGF-beta were discovered by Dietz and colleagues. His group subsequently showed that losartan can halt the dangerous ballooning of the aorta caused by abnormal TGF-beta in patients with Marfan and Loeys-Dietz syndromes
http://www.eurekalert.org/pub_releases/2013-07/jhm-jhr071813.php
http://www.hopkinschildrens.org/Aortic-Aneurysm-Growth-Treatment-in-Marfan-Syndrome.aspx

Mathematical model of dual targetting cancer therapy

data based on melanoma.
Title:  Evolution dynamics of Cancer in response to targetted combination therapy.
The word "cure" actually appears here.    Though it may not apply to BC but the logic used is generally applicable and fairly interesting:
http://elife.elifesciences.org/content/2/e00747


Another article on heterogeneity of breast cancer from serum CTC:

J Intern Med. 2013 Aug;274(2):137-43. doi: 10.1111/joim.12047.

Circulating tumour cells: insights into tumour heterogeneity.

http://www.ncbi.nlm.nih.gov/pubmed/23844916
http://onlinelibrary.wiley.com/doi/10.1111/joim.12047/full


Another  article on the history of "Cell Kill" Adjuvant chemotherapy approaches of last 50 years, and inflammation-cancer link

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691519/

"DIGGING DEEPER: GROWTH PARAMETERS OF SOLID TUMORS CAUSE CHEMOTHERAPY RESISTANCE"

Nature's review of targetted BC medicine in clinical trials

Article in Nature:

"Emerging targeted agents in metastatic breast cancer"

Dimitrios Zardavas, José Baselga & Martine Piccart

Abstract

The same article has list of targetted medicine for drugs targetting microenvironment:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T3.html

targetting BC cells in general:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T1.html

targetting BC stem cells:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T2.html


Even a result table for trials which has been completed:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T4.html

Add up CR+PR+SD divide it with total n to get how good early results are.   Unfortunately no progression free survival information on the table.    A  cursory look at the table tells me the best, by head and legs are palbociclib for ER+ women with (PR+SD = 26 among 34 patients):

Letrozole ± PD 033299181

CDK1, CDK6

These are very interesting especially if they work for TN women, or could figure out accurate dx test to identify the people who might benefit better:

Cabozantinib222

MET, VEGFR2

Dovitinib60

FGFR1, VEGFR, PDGFRβ, KIT, FLT3

Vorinostat (+ ixabepilone)225

HDAC

I

36

All

All

2

6

16

Bosutinib231

SRC

II

73

All

Chemotherapy and/or hormone therapy

0

4

24

BKM120217	PI3K	I	9	All	Any	0	1	5
BKM120 (+ letrozole)218	PI3K	I	51	ER+/HER2–	AI	1	1	13

If someone's interested in any of these products, go back to Table 1 or table 2 or table 3, look for the other drugs with similar targets.    For example, if you are interested in PD 0332991 (palbociclib), go back to table 1 to look for other CDK targetting compounds.   Law of economics would suggest that those drugs will compete well and/or completement well with palbociclib.   No guarantee of course.

(Clinical Trial Conjecture I: The Conjecture of Achilles Heel:   As soon as someone proved that Achilles has a weakness in his heel, all the arrows from Troy's side is gonna go to the heel until Achilles, the invincible becomes vincible and his heel will look like porcupine.)

Notice also the drugs for whom the results are not so good or even abysmal.    Some are not good but has Complete response, that's still interesting.   Some may need to pair up with other drugs to perform well.   Some may need better diagnostic test to target better.     Remember HIV became treatable with a drug cocktail and cancer may be treatable too from a targetted drug cocktail.   So not to write any out, but a lot of work needs to be done if so many phase I/II trials are not turning out gold.  

There are probably many more drugs whose results are not in yet, or are dropped due to poor results, poor recruitment or for other technical or business reasons.     That is the invisible story of breast canc er clinical research.   We need more open data, more better designed drug clinical tests for new agents.

Natada in inspire shared these:
http://www.inspire.com/groups/advanced-breast-cancer/discussion/targetd-therapy-clinical-trial-for-breast-cancer-stem-cells-and-mbc/


Nice figure here:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_F1.html#figure-title
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_F2.html

I might as well go into the Clinical Trial Conjecture II:
The Conjecture of Innovation being proportional to iteration speed:   The shorter time between lab bench to FDA approval, the faster the disease will get an effective cure.  and vice versa.

Comment:  neoadjuvant trials like ISPY-2 are going to accelerate the pace of BC innovation
http://clinicaltrials.gov/show/NCT01042379


and the Breast Cancer Clinical Trial Conjecture III:
The Conjecture of Good being the Enemy of the Best:  Adjuvant usage of ok drugs for early stage breast cancer may save lives, but they reduce the incentive for actual great drugs that cures late stage breast cancer.

Comment: This is caused by the unique character of breast cancer where early stage breast cancer rarely kills but are extremely common, yet because late stage breast cancer remains a killer, there are vastly more incentive to develop ok drugs for adjuvant use, vs great drugs for late stage bc patients.   It seems a lot of pharma would rather repurpose a proven ok cancer drug (developed for a different cancer), spend 10 years and 100s of millions to test its efficacy for breast cancer in adjuvant settings, rather than starting from scratch on new drugs that could potentially cure MBC.    You could argue the latter is more risky, or you could argue that the former gets better pay-off in adjuvant use on less risk.

HR+ breast cancer flipping biomarkers

I have reason to suspect HR+ breast cancer (even stage IVers) is going to get a cure (90+% 5 year survivability) pretty soon, within a few years.    But cancer is an evolutionary disease.   So I'm interested in understanding the phenomenon of HR+ BC flipping into triple negative type BC.

http://breast-cancer-research.com/content/14/3/r71



http://www.medscape.com/viewarticle/805441_4

Total of 11 triple negative patients.  5 of whom were stage III at start of study.   6 of whom were either NED stage IV or maybe stage II.    Total of 2 relapsed.   Very small study.

Quote from this article:  To gain a better understanding of the targets of TM, we measured circulating markers of angiogenesis. SDF1 and its receptor CXCR4, involved in angiogenesis and metastatic progression, may have a role in EPC recruitment.^[36,37] In breast cancer patients, expression of SDF1 has been inversely correlated with survival.^[38] In our study, SDF1 decreased with copper depletion but increased before relapse. Likewise, MMPs increased in patients before relapse. MMPs regulate tumor growth and invasion^[36] and provide a permissive bone marrow niche to facilitate mobilization of progenitor cells.^[39] Our observations suggest that SDF1 and MMPs may have important roles in metastatic progression.

Though a randomized clinical trial is necessary to assess survival, efficacy measures were promising. Of 11 triple-negative patients on study, only 2 relapsed. One patient did not adequately copper-deplete despite incremental dose increases. The other patient progressed within 2 months of TM therapy, suggesting that active neoangiogenesis was occurring at the time of enrollment, which could not be halted due to delayed effects of copper depletion. We are cautiously optimistic about the low incidence of relapse and have extended the study to 6 years in selected patients. Two stage-4 NED triple-negative patients remain disease-free at 65 and 49 months on TM therapy, which is encouraging given the dismal median survival of 9 months in metastatic triple-negative patients

http://www.ncbi.nlm.nih.gov/pubmed/23686707

http://www.ncbi.nlm.nih.gov/pubmed/22825030

http://www.ncbi.nlm.nih.gov/pubmed/22510516



I'm reading this with interest because ovarian cancer is linked and related to some type of TN breast cancer
http://www.cancernetwork.com/ovarian-cancer/content/article/10165/2148722

Should Cancer Clinical Trial Data be Open Sourced?

Every year hundreds of new agents are touted as potential cure for metastatic breast cancer and other deadly cancers.   Few got into early stage human trials often by small startup companies.   Some do well, some do ok, some do badly.     Big Pharmas could afford to buy dozens of these small startup companies.   And mostly these new agents are never heard from again.  The public has no idea which ones do well, ok, or badly.  These results were sealed,  should they be somehow accessible to public?   

http://www.nytimes.com/2013/06/30/business/breaking-the-seal-on-drug-research.html?pagewanted=all

Several related issues about metastatic breast cancer funding and drug development are discussed here:

http://community.breastcancer.org/forum/73/topic/806626?page=2#idx_45

Etacstil was once a promising breast cancer drug that performed ok or better in early stage human trial, but the company was acquired by BMS, and its early stage human trial's data was never published.   When its development and clinical trial was abandoned and existant tablets destroyed by BMS, patients who were doing well on that drug sued to try to stay on the drug, but to this day, results on its performance IS NOT accessible by public:

http://community.breastcancer.org/forum/8/topic/806200

This movement towards data openness started in Flu treatment, but will not end there.   

Also in today's news, another *attempted* acquisition of a big cancer drug maker onyx by other even bigger drug maker amgen.   How does drug development for MBC and other deadly cancers changes with this kind of consolidation going on all the time?   Which project (on either side) will live, which project will die?   What happens to the acquired clinical trial data under the new overlord?   

http://www.latimes.com/business/money/la-fi-mo-onyx-pharmaceutical-amgen-20130701,0,2996281.story

Big Pharma, little pharma are like any other business.   When the public hold out money without asking questions or putting in check/balances, it will ALWAYS be taken advantage of.

My question is:

How should we help in finding a metastatic breast cancer cure?   What change should we make in our laws and healthcare strategy?   Who should we recruit to make such changes?   FTC and/or  FDA?  researchers?  economists?  computer geeks?  media?

http://www.xconomy.com/national/2013/07/29/pharma-fails-credibility-test-misses-opportunity-on-transparency/?utm_source=rss&utm_medium=rss&utm_campaign=pharma-fails-credibility-test-misses-opportunity-on-transparency

Interesting news this week

Silver makes antibiotics much more effective:
http://www.scientificamerican.com/article.cfm?id=silver-makes-antibiotics-thousands-of-times-more-effective

Osteoporosis Drug Stops Growth of Breast Cancer Cells, Even in Resistant Tumors

http://community.breastcancer.org/forum/8/topic/806200

This is preclinical.  Some interesting comments by the author of bazedoxifene study, mentions other SERD (like Faslodex) that actually tested well in early clinical trials 10 years ago, but was shut down.

"about 10 years ago our lab identified and developed another SERD that is just as effective in vitro, could be administered orally, worked great in animal models, and, when Dupont took it into a small investigator initiated trial, worked well even in patients who had progressed during therapies targeting estrogen receptor.  So well, in fact, that when BMS bought Dupont and assumed that a paint company knew nothing about healthcare and closed the trial, the patients' Drs sued to keep them on the trial.  BMS responded by destroying 4 million tablets."     I'm trying to figure out that little bit of history.

Anti Cancer goo secreted by naked Mole Rats  Pretty interesting:

http://www.medicalnewstoday.com/articles/262236.php

CFI-400945 is applying for clinical trial:

http://life.nationalpost.com/2013/06/18/breakthrough-anti-cancer-drug-takes-direct-aim-at-tumours-canadian-u-s-researchers-say/

This drug is from the same UCLA lab (Dr Slamon) that gives us Herceptin and Palbociclib.   If this drug and other drugs from this UCLA Canadian Chinese partnership are any thing like Herceptin or Palbociclib, then, well, maybe i could stop writing this blog happily.  

Quote from this article:

“I cannot promise you that it will work,” he said of the experimental drug, “because in advanced human cancer there are many other questions that we have not got answers to.

“But we promise you this is the beginning,” said Mak, his voice breaking with emotion. “There will be another drug that we will be filing for [approval] next year — and next year and next year — until we get this done.”

It’s taken about 100 researchers in Toronto, L.A. and China to develop CFI-400945 at a cost so far of about $40-million, said Mak, standing beside a copy of the 4,300-page application submitted to the FDA, the height of about five Toronto phone books.

That money all came from non-government sources, raised through 10 years of fundraising walks to end women’s cancers, and private and corporate donations.

...

http://www.ncbi.nlm.nih.gov/pubmed/23829549

   

  

Supreme Court Strikes Down Gene Patents

Nature can not be patented:
http://www.boston.com/business/technology/2013/06/13/court-says-human-genes-cannot-patented/56BCnX2hTvDXSOedSkOy0N/story.html

But some processes could:
http://www.startribune.com/lifestyle/health/211446711.html

"However, Jeffrey Rosenfeld, a researcher and assistant professor at the University of Medicine and Dentistry of New Jersey, said the ruling is good news for researchers, who now will be able to sequence genes to try to better understand diseases and to create new treatments — without fear of being sued by companies such as Myriad.

"Their monopoly is gone. The method patents basically are completely irrelevant," Rosenfeld said.

He said diagnostic testing companies now could sequence genes linked to breast cancer or other diseases and use the information to develop diagnostic tests that use different methods than Myriad's. Likewise, he said, "scientists can now research freely without fear of being sued."

Sad really.   Is the gene patent troll problem as bad as in software?  

Rucaparib Parp Inhibitor Showing High Disease Control Rate In Early Test

http://meetinglibrary.asco.org/content/115538-132

Disease control >12 week

Angelina Effect

In one year, I expect the prophelactic mastectomy rates would double if not triple.   I also expect the rates of women asking for BRCA tests to double and the maker of BRCA tests is going to have a stellar year.

Here's why I am not thrilled:   

1.  BRCA tests are expensive and provides very little information for either research or treatment.   95% don't have these known BRCA mutations, 10% would develop BC anyway.   Full gene sequencing provides much more information for research and treatment someday, and its price is just a bit more than BRCA tests.   Yet I see NO articles making this point.     Taxpayers and insurers have NO obligation to foot the bill for BRCA tests, but every reason to support more research in full gene sequencing.

2.   Breast cancer, specificly metastatic breast cancer has no cure.   This is the foundamental justification for Angelina's decision.   More money needs to go to research and more research into metastatic BC, not into unnecessary and expensive BRCA gene tests.   Again I do not see anyone making these point.

Angelina Effect could be really positive if Angelina Jolie could direct attention to support for MBC research.   Totally wasteful if it just ends up with more women clamouring for BRCA gene tests, and getting a false sense of security when BRCA tests show negative for a few known mutations and forget about the threat of MBC.

PD991 or Palbociclib Receives FDA Breakthrough Designation

http://www.fiercebiotech.com/press-releases/pfizers-palbociclib-pd-0332991-receives-food-and-drug-administration-breakt

Copper Reduction for TN

If they are able to keep even 1/2 of the metastatic TNBC folks alive for a few years, that's pretty awesome:
http://weill.cornell.edu/news/releases/wcmc/wcmc_2013/02_13_13.shtml

Their clinical trial is expanding.

NeuroBlate on recurrent glioblastoma multiforme

http://www.medpagetoday.com/TheGuptaGuide/Oncology/38288

"In the first-in-man phase I study, published online in the Journal of Neurosurgery,median survival of 10 patients treated with the NeuroBlate Thermal Therapy System was 316 days."

Doubling the survival of a very aggressive brain cancer.   Could it be used for other type of brain tumor as well?   

Circulating Tumor DNA: Proof of concept

http://www.nejm.org/doi/full/10.1056/NEJMoa1213261

29/30 metastatic patient sees their CT dna above normal.   Wow!

Great Clue Mystery

Cancer, Immune system, Brain, these are arguably the 3 enduring high stake mysteries in medicine.  

I put Cancer first, because it is the one mysteries with dead bodies all over the carpet.   And thousands of characters, some are suspected ring leaders, some are accomplices, some are panicked onlookers, some are striking security guards.       

Then there are researchers, like detectives, some focus on "who dunnit", some on "how dunnit", some on "protecting the innocent and preventing carnage".    They need all the help they could get.

This new development from Minnesota implicates a well hidden ring leader that may lead to a new strategy:

http://medicalxpress.com/news/2013-02-enzyme-breast-cancer-mutations.html#jCp

While this NIH development seems to study the "how dunnit" mystery that metabolism affects cancer

http://www.nih.gov/news/health/feb2013/nci-05.htm

Interesting new development

BCO members shared these research, new approaches and fresh understanding of the puzzle that is cancer:

Gold nanoparticle in HDL used to target lymphoma cancer cells
http://www.sciencedaily.com/releases/2013/01/130121161915.htm

New understanding of how Beta blockers' effect on cancer:
http://www.sciencedaily.com/releases/2013/01/130129121843.htm

Metastasis pathways:
http://www.eurekalert.org/pub_releases/2013-01/cu-cbd011813.php
http://www.sciencedaily.com/releases/2013/01/130127134214.htm

Review article and clinical trials

http://www.asco.org/ASCOv2/Home/Education%20&%20Training/Educational%20Book/PDF%20Files/2012/zds00112000028.PDF

It mentions also BKM120 and other new drugs

http://www.dovepress.com/new-and-emerging-treatments-for-estrogen-receptor-positive-breast-canc-peer-reviewed-article-TCRM

Pancreatic cancer gets a new agent

half as few death for one of the most aggressive cancers.   Yeah!
http://www.medscape.com/viewarticle/778018

Presentation on Korean/Asian BC incidences

This presentation includes BC incidence, age distribution and other information on Korea, Japan, China, Israel, Pakistan,India, Philipines and other Asian countries.

What most jump out to me is how the Korean/Japanese/Chinese have a lower incidence but younger demographics of BC.   How Philipines and Pakistan and Israel have the higher rates of BC.    Interesting for people who want to learn from other cultures about what to do what not to do.

http://www.pitt.edu/~super4/41011-42001/41081.pdf

PD-991 may qualify for the Fast track

Pfizer wants to fast track this miracle drug based on strong phase II results:
http://www.pfizer.com/files/news/asco/pd_0332991_cdk_4_6_inhibitor_fact_sheet.pdf
http://www.bloomberg.com/news/2013-01-10/pfizer-may-push-5-billion-breast-cancer-hope-for-ruling.html

There are more drugs in the pipeline that is based on the same principle from other drug makers

http://www.kantarhealth.com/blog/oncology/stephanie-hawthorne/2012/12/06/CDK_Inhibition_The_Next_Big_Thing_in_ER_Breast_Cancer_Impresses_at_SABCS_2012

Last December news about PD-991:  26 month PFS (PD-991) compared with <10 months PFS with Femara alone
http://killerboob.blogspot.com/2012/12/pd-991-with-femara.html

Foundation Medicine Got More from Bill Gates

Not full-genome sequencing.  but much better than Oncotype or Mammotype.   Costs similar around $5k.

Complete Genomics is another pioneer complete sequencer

http://www.boston.com/businessupdates/2013/01/08/bill-gates-invests-foundation-medicine-which-uses-genome-data-for-cancer-diagnostics/BtipX6STIA5prjmrjJkHzI/story.html

A new angle of attack from Japan via T-cell

T-cell attack from Japan