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Using metformin?

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Post Options Post Options   Thanks (0) Thanks(0)   Quote blen9 Quote  Post ReplyReply Direct Link To This Post Posted: Oct 26 2011 at 10:20pm
Hi Blair,

Thanks for your reply....Yes, it is the only medication I am taking. I am not diabetic though. And it has been months since chemo. I'm just worried and was wondering if other people are suffering from similar symptoms while on the trial/off-label.

Cheers
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Oct 27 2011 at 11:40pm

FYI: Update

Re; U.S.: NCT: 01101438    Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer
Have been checking Clinicaltrials.gov and still don't see any the US sites for this trial.

See posts on this matter of October 20,2011.

I plan to contact the person I spoke/emailed around Oct 20 next week if US sites still not showing.

Grateful for today.............Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Oct 31 2011 at 8:01pm
FYI:

SUCCESS!    USA metformin clinical trial sites now posted on:

http://clinicaltrials.gov     ( breast cancer    metformin placebo)
NCT: 01101438    Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer

There are about 196 clinical trial sites in USA.


With positive and caring thoughts for all,

Grateful for today............Judy

-----------------
FYI: There are at least 3 forum sites on metformin. Am posting this info on all three.
            Metformin Trials
            Using metformin.
            Asking questions on metformin trials.
            
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Nov 28 2011 at 7:56am

Metformin Prevents Tumors From Growing In Human Cultures

An inexpensive drug that treats Type-2diabetes has been shown to prevent a number of natural and man-made chemicals from stimulating the growth of breast cancer cells, according to a newly published study by a Michigan State University researcher. 

The research, led by pediatrics professor James Trosko and colleagues from South Korea's Seoul National University, provides biological evidence for previously reported epidemiological surveys that long-term use of the drug metformin for Type-2 diabetes reduces the risk of diabetes-associated cancers, such as breast cancers. 

The research appears in the current edition of PLoS One

"People with Type-2 diabetes are known to be at high risk for several diabetes-associated cancers, such as breast, liver and pancreatic cancers," said Trosko, a professor in the College of Human Medicine's Department of Pediatrics and Human Development. "While metformin has been shown in population studies to reduce the risk of these cancers, there was no evidence of how it worked." 

For the study, Trosko and colleagues focused on the concept that cancers originate from adult human stem cells and that there are many natural and man-made chemicals that enhance the growth of breast cancer cells. 

Using culture dishes, they grew miniature human breast tumors, or mammospheres, that activated a certain stem cell gene (Oct4A). Then the mammospheres were exposed to natural estrogen - a known growth factor and potential breast tumor promoter - and man-made chemicals that are known to promote tumors or disrupt the endocrine system. 

The team found that estrogen and the chemicals caused the mammospheres to increase in numbers and size. However, with metformin added, the numbers and size of the mammospheres were dramatically reduced. While each of the chemicals enhanced growth by different means, metformin seemed to be able to inhibit their stimulated growth in all cases. 

"While future studies are needed to understand the exact mechanism by which metformin works to reduce the growth of breast cancers, this study reveals the need to determine if the drug might be used as a preventive drug and for individuals who have no indication of any existing cancers," he said. 

"Though we still do not know the exact molecular mechanism by which it works, metformin seems to dramatically affect how estrogen and endocrine-disrupting chemicals cause the pre-existing breast cancers to grow." 


Edited by 123Donna - Dec 02 2011 at 8:07am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote TNinTN Quote  Post ReplyReply Direct Link To This Post Posted: Nov 28 2011 at 8:09am
Great article. Thanks, Donna!
Wife age 53@dx TN IDC Stage IIA 7/10; BRCA1&2 Neg; BROCA Neg; LN Neg; taxol+cisplatin+/-RAD001x12(clinical trial); lumpectomy 12/10;ACx4; 33 Rads complete 4/11; NED 5/5/11
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 04 2011 at 1:14pm
I hope we see some talk/study results at the Breast Cancer conference in San Antonio this week about Metformin.

New 'Achilles' Heel' In Breast Cancer: Tumor Cell Mitochondria

Researchers at the Kimmel Cancer Center at Jefferson have identifiedcancer cell mitochondria as the unsuspecting powerhouse and "Achilles' heel" of tumor growth, opening up the door for new therapeutic targets in breast cancerand other tumor types. 

Reporting in the online Dec.1 issue of Cell Cycle, Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Thomas Jefferson University, and colleagues provide the first in vivo evidence that breast cancer cells perform enhanced mitochondrial oxidative phosphorylation (OXPHOS) to produce high amounts of energy. 

"We and others have now shown that cancer is a 'parasitic disease' that steals energy from the host -- your body," Dr. Lisanti said, "but this is the first time we've shown in human breast tissue that cancer cell mitochondria are calling the shots and could ultimately be manipulated in our favor." 

Mitochondria are the energy-producing power-plants in normal cells. However, cancer cells have amplified this energy-producing mechanism, with at least five times as much energy-producing capacity, compared with normal cells. Simply put, mitochondria are the powerhouse of cancer cells and they fuel tumor growth and metastasis. 

The research presented in the study further supports the idea that blocking this activity with a mitochondrial inhibitor -- for instance, an off-patent generic drug used to treat diabetes known as Metformin -- can reverse tumor growth and chemotherapy resistance. This new concept could radically change how we treat cancer patients, and stimulate new metabolic strategies for cancer prevention and therapy. 

Investigating the Powerhouse 

Whether cancer cells have functional mitochondria has been a hotly debated topic for the past 85 years. It was argued that cancer cells don't use mitochondria, but instead use glycolysis exclusively; this is known as the Warburg Effect. But researchers at the Jefferson's KCC have shown that this inefficient method of producing energy actually takes place in the surrounding host stromal cells, rather then in epithelial cancer cells. This process then provides abundant mitochondrial fuel for cancer cells. They've coined this the "Reverse Warburg Effect," the opposite or reverse of the existing paradigm. 

To study mitochondria's role directly, the researchers, including co-author and collaborator Federica Sotgia, Assistant Professor in the Department of Cancer Biology, looked at mitochondrial function using COX activity staining in human breast cancer samples. Previously, this simple stain was only applied to muscle tissue, a mitochondrial-rich tissue. 

Researchers found that human breast cancer epithelial cells showed amplified levels of mitochondrial activity. In contrast, adjacent stromal tissues showed little or no mitochondrial oxidative capacity, consistent with the new paradigm. These findings were further validated using a computer-based informatics approach with gene profiles from over 2,000 human breast cancer samples. 

It is now clear that cancer cell mitochondria play a key role in "parasitic" energy transfer between normal fibroblasts and cancer cells, fueling tumor growth and metastasis. 

"We have presented new evidence that cancer cell mitochondria are at the heart of tumor cell growth and metastasis," Dr. Lisanti said. "Metabolically, the drug Metformin prevents cancer cells from using their mitochondria, induces glycolysis and lactate production, and shifts cancer cells toward the conventional 'Warburg Effect'. This effectively starves the cancer cells to death". 

Personalized Treatment 

Although COX mitochondrial activity staining had never been applied to cancer tissues, it could now be used routinely to distinguish cancer cells from normal cells, and to establish negative margins during cancer surgery. And this is a very cost-effective test, since it has been used routinely for muscle-tissue for over 50 years, but not for cancer diagnosis. 

What's more, it appears that upregulation of mitochondrial activity is a common feature of human breast cancer cells, and is associated with both estrogen receptor positive (ER+) and negative (ER-) disease. Outcome analysis indicated that this mitochondrial gene signature is also associated with an increased risk of tumor cell metastasis, particularly in ER-negative (ER-) patients. 

"Mitochondria are the 'Achilles' heel' of tumor cells," Dr. Lisanti said. "And we believe that targeting mitochondrial metabolism has broad implications for both cancer diagnostics and therapeutics, and could be exploited in the pursuit of personalized cancer medicine." 
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 08 2011 at 9:28pm
This is from SABCS:

On Dec. 7, an early-morning press briefing has been scheduled for investigators to outline findings of four noteworthy studies.

- Swedish researchers will report that diabetes and obesity after age 60 are risk factors for breast cancer. Low lipids also increased risk, but high lipids did not in their study comparing medical records of more than 23,000 women. Similarly, risk went up with use of the diabetes drug glargine but down with metformin.

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 10 2011 at 1:34am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote TNinTN Quote  Post ReplyReply Direct Link To This Post Posted: Dec 10 2011 at 7:06am
Does this mean that we should not be taking so much Lipitor and/or did they say what your lipids range should be? Our PCP is very aggressive in keeping our lipids low with statin drugs. Susan has been taking Simvastatin for years. I don't recall what her levels are, but they are always well below the levels that are considered problematic.
 
Susan's surgery cancerversary was yesterday, 12/9 (one year - hooray!Smile), and she has been in the Metformin trial for about six months now. We go back to Vanderbilt next Wednesday for follow-up, labs, mammogram, etc., so I'll try to remember to ask about this.
 
Martin


Edited by TNinTN - Dec 10 2011 at 7:22am
Wife age 53@dx TN IDC Stage IIA 7/10; BRCA1&2 Neg; BROCA Neg; LN Neg; taxol+cisplatin+/-RAD001x12(clinical trial); lumpectomy 12/10;ACx4; 33 Rads complete 4/11; NED 5/5/11
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 10 2011 at 10:01am
Martin,

I don't know.  I've been looking for any reports or summaries released on Metformin from the SABCS but haven't found any yet.  I'll post if I find any.

Donna
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote TracyAMac Quote  Post ReplyReply Direct Link To This Post Posted: Dec 20 2011 at 10:02pm
Martin, I love your term "cancerversary". Contrats to you and Susan!

 Fortunately I was able to continue the Metformin trail last week including day of surgery. Surgery was at the same hospital the trial  with Dr. Pam Godwin

Tracy in Toronto
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mindy555 Quote  Post ReplyReply Direct Link To This Post Posted: Dec 21 2011 at 6:08pm
I plan to talk to my PCP about metformin.   He's another out-of-the-box thinking doc, and a very good one.

My last fasting blood test with him (at least 2 years ago) proved to be at the highest end of normal.  My Dad,  his mother and her sisters were all type II diabetic.

Thanks for the tremendous contribution of information.

Blessings!
Mindy

I pulled that blood work.. it's been almost 3 years ago.  I was a few points out of range on the high end.

Although at my PET scan my blood sugar was normal.  I'm overdue to have a complete blood panel done anyway.


Edited by mindy555 - Dec 21 2011 at 6:23pm
Dx July 2011 56 yo
Stage I IDC,TN,Grade 3
Grew to Stage IIa- No ev of node involve- BRCA1+ chondroid metaplasia
Daughter also BRCA1+
Mass grew on Taxol
FEC 6x better
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 21 2011 at 6:31pm
I wish more studies were highlighted or results released at the SABCS a few weeks ago.  
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote K in Sugar Land Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2012 at 2:06pm
I spent the day at the Vanderbilt Breast Center yesterday and I am now, as of today, participating in the trial.  It was a pleasure to meet with Dr. Ingrid Mayer and the staff at Vanderbilt.  I was impressed with the level and quality of care I received and they all treated me like I was royalty.  No kidding. 
 
Two tips I picked up about anyone taking metformin: 
 
It is recommended to eat something every four hours.  Do not skip any meals.
 
I was advised that metformin should be stopped about three days before and after receiving IV  contrast that is used in CT scans.  This is important to help avoid lactoacidosis.  I need to do more research myself on lactoacidosis, but I understand it can be life-threatening, so halting metformin for a few days before and after receiving IV contrast definitely needs to be on our radar screens.
Dx IDC TNBC MDA2/11 age 51 T2N0M0 Grd 3 4.8cm BRCA- vitD22 Taxol 12wk FAC once 3 wk for 12 wk Complete chemo8/11 Tumor not seen on scans Lumpsurgery 0/4 nodes9/11 pCR 30rads done11/11 NED vitD3903/12
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Post Options Post Options   Thanks (0) Thanks(0)   Quote dmwolf Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2012 at 4:33pm
Hey, you had a pCR, K!  Why are you entering a trial?  Your chance of recurrence is almost nil.
Metformin is not completely benign as a drug, from what I hear, and there isn't much evidence in favor of taking it if you aren't extremely overweight and/or diabetic.  Why take it if your chance of recurrence is so low?

DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote tania Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2012 at 5:40pm
"Almost" nil.  Chance of recurrence is "so low".....
 
I, for one, am not willing to give this thing a second chance at me.  I definitely fall in the camp of throw the book at it.  I was stage 1, no nodes, RCB of 1 after neodjuvant Gemzar/Carboplatin and still did 4X TC adjuvant. My oncologist and the endocrinologist at Stanford felt that this drug had little downside and some possible, while not proven, benefit that they were willing to prescribe off label.  I came to her with alot of ideas and research and this is the only one she felt had enough potential vs. risk that she thought if worth doing. There does seem to be alot of interest in the research community about metformin.  Just look how much has been posted here since I started this post last summer.
 
The exact quote from my oncologist was "it isn't going to hurt you, and it might possibly be beneficial".  Who knows if it will turn out to have been a good thing or not.  It does make me feel like I am doing something to fight back.
 
I have been on the drug since late August. Have had a couple of blood panels to monitor and my glucose is in the same range as before taking. No liver or kidney changes.  I am normal weight with no signs or family history of diabetes.  I have diarrhea sometimes.  I have some of the symtoms that others have mentioned - sweats, palpitations.  Who knows if related, but I bet the surgical menopause and general survivor anxiety could account for all of the above!
 
I wouldn't do this without being under doctor care and supervision. I do echo the warnings of go off before a CT scan.  I almost had to reschedule one, but they pulled labs to check liver function, which was fine.  I generally hold off while fasting.
 
dmwolf - you always post such good info and research.  What specifically makes you so hesitant about metformin?  What do you know that we should all consider?
DX 10/2010. 1.5cm, no nodes, grade 2. BRCA1+
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Post Options Post Options   Thanks (0) Thanks(0)   Quote kidzrn Quote  Post ReplyReply Direct Link To This Post Posted: Mar 27 2012 at 11:44pm
for those taking metformin, how much are you taking...I have heard many different things...500mg  3 x per day? is that just for diabetics or non diabetics as well...I have stage 4 tnbc, ned but want plan b thanks christi
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2006,TNBC,Gr3 dbl mast, 4AC/4T {NED 4/07}, Lung Met 4/08, Carbo, Avastin, Taxol/Taxotere (CAT)x4, Lung Surgery 9/08, 4 CAT, then Avastin every 3 wks...NED 2/09, 2/10, 6/10, 10/10 Scans 4/11
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Post Options Post Options   Thanks (0) Thanks(0)   Quote TNinTN Quote  Post ReplyReply Direct Link To This Post Posted: Mar 28 2012 at 7:22am
The trial dosage for my wife, Susan, is 850mg twice daily - of course we don't know if she is getting Metformin or the placebo.
 
Martin
Wife age 53@dx TN IDC Stage IIA 7/10; BRCA1&2 Neg; BROCA Neg; LN Neg; taxol+cisplatin+/-RAD001x12(clinical trial); lumpectomy 12/10;ACx4; 33 Rads complete 4/11; NED 5/5/11
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Post Options Post Options   Thanks (0) Thanks(0)   Quote tania Quote  Post ReplyReply Direct Link To This Post Posted: Mar 28 2012 at 12:48pm
850mg twice a day.  I am not in the trial, but my oncologist is following the same dosage as the trial. I was able to get her to prescribe off label so to be sure to be getting the drug.
DX 10/2010. 1.5cm, no nodes, grade 2. BRCA1+
Neoadjuvant chemo gem/carb/parpi trial.
Bilateral mastectomy 4/2011
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Post Options Post Options   Thanks (0) Thanks(0)   Quote TracyAMac Quote  Post ReplyReply Direct Link To This Post Posted: Apr 01 2012 at 10:26pm
Hi Christi
I am taking the same dose as Martin's wife Susan -  850mg 2x/day as part of the clinical trial(or placebo - hopefully not!!!).
I understand that diabetics are excluded from the trial- the main rational for the trial is that there was evidence in Phase I and II trials  that many diabetic women on Metformin with BC (and also under active BC treatment) were experiencing higher survivability/lower recurrence rates compared to non-diabetic women.

Tracy in Toronto
TN&non-TN tumors April/10 Gr3&2;1 metaplastic
Rmast.1/9 nodes w/isolated t.cells
Taxotere&Cytoxan x6
Bone cancer 1980 age17;surgery&chemo AC+Methotrexate
BRCA-ve
On hormone therapy & Metformin Trial
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