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Has any of your all oncologist said anything about Metformin as treatment for bc

Unhappy
Posts: 88
Joined: Dec 2012

I have heard that it may make a difference .Just wondering if anyone else had heard anything about it.

New Flower
Posts: 3914
Joined: Aug 2009

Review of this topic

http://www.medpagetoday.com/MeetingCoverage/SABCS/36442Primary source: San Antonio Breast Cancer Symposium

Source reference:
Cazzaniga M, et al "The effect of metformn on apoptosis in a breast cancer presurgical trial" SABCS 2012; Abstract PD03-01.

Additional source: San Antonio Breast Cancer Symposium
Source reference:
Kalinsky K, et al "Presurgical trial of metformin in overweight and obese, multiethnic patients with newly diagosed breast cancer" SABCS 2012; Abstract PD03-03.

Additional source: San Antonio Breast Cancer Symposium
Source reference:
Dowling RJO, et al "Analysis of tumor cell signaling in response to neoadjuvant metformin in women with early-stage breast cancer" SABCS 2012; Abstract PD03-05.Amant F, et al "Breast cancer in pregnancy" Lancet 2012; 379: 570–79.

Additional source: The Lancet Oncology
Source reference:
Cardonick E "Treatment of maternal cancer and fetal development" Lancet Oncol 2012.

 

SIROD's picture
SIROD
Posts: 2116
Joined: Jun 2010

Metformin Role in Breast Cancer Still Unclear

By Charles Bankhead, Staff Writer, MedPage Today

 

Published: December 13, 2012

 

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

 

SAN ANTONIO -- Clinical trials of the diabetes drug metformin in breast cancer yielded a few possible clues to anticancer activity but little else, according to a series of reports.

The largest of three trials showed no significant effect on tumor-cell apoptosis in women who received metformin prior to surgery. Higher apoptotic activity was observed in patients without insulin resistance compared with the insulin-resistant subgroup.

Results of the other two trials hinted at host-specific factors that might influence the drug's effect on apoptosis and cell proliferation, as reported at the San Antonio Breast Cancer Symposium.

In a review of the three studies and others included in a poster session, Michael N. Pollak, MD, borrowed a line from Winston Churchill and characterized the status of metformin research in cancer as "approaching the end of the beginning."

"We're not really yet at the middle or concluding phases of the research, because there are a lot of unanswered questions, and some of those questions have become clear from the review of the posters today," said Pollak, of McGill University in Montreal.

The rationale for investigating the anticancer potential of metformin has as its origin observations that diabetic patients treated with metformin had a lower prevalence of cancer compared with diabetic patients treated with other medications or no medication.

Laboratory studies have suggested multiple mechanistic pathways by which metformin might inhibit tumor growth or proliferation, including Stat3, AMP kinase, and insulin receptor kinase, said Pollak. However, studies involving laboratory models also have resulted in higher metformin concentrations than those achieved with conventional dosing in patients.

"Insulin -- or something correlated with insulin -- influences prognosis, but early trials have shown perturbations of insulin by metformin that are small in magnitude and that vary between subjects," said Pollak. "Other less-explored candidate metformin effects on the host include changes in inflammatory cytokines, serum kinase-activating activity, and others."

Moreover, placebo-controlled studies have demonstrated unexpected increases in the proliferation marker Ki-67 between baseline and surgical biopsies in placebo-treated patients. The findings might represent an artifact or suggest that surgery somehow influences tumor proliferation, Pollak continued.

As described in one of the poster presentations, Italian investigators evaluated cancer-cell apoptosis in 88 breast cancer patients who were randomized to metformin or placebo for 4 weeks prior to surgery for early breast cancer. Apoptosis was assessed by TUNEL assay in biopsy samples obtained before randomization and immediately prior to surgery.

Apoptosis was similar between groups at baseline (4% and 3% in the metformin and placebo arms, respectively) and increased significantly (P<0.0001) in both arms prior to surgery (10% and 8%, respectively). TUNEL levels at surgery did not differ significantly between groups, according to Giancarlo Pruneri, MD, of the European Institute of Oncology in Milan.

Investigators found borderline-significant evidence (P=0.1) of interaction between TUNEL and homeostasis model assessment (HOMA), a measure of insulin resistance. Patients who were not insulin resistant (HOMA <2.8) had a TUNEL level of 10% with metformin versus 6% with placebo (P=0.05).

In contrast, women with insulin resistance (HOMA ≥2.8) had a median TUNEL value of 6% with metformin and 9% with placebo (P=0.3).

The data also showed significant correlation between the proliferation factor Ki-67 and TUNEL at baseline and surgery (P<0.0001).

Another small presurgical study showed no effect of metformin on tumor proliferation, as reflected by levels of Ki-67. The study involved 35 overweight and obese women (body mass index [BMI] >25) with early breast cancer (N=25) or ductal carcinoma in situ (N=10).

The patients started metformin 2 to 4 weeks before surgery (median duration 22 days), and the study's primary endpoint was the change in Ki-67 activity from baseline to surgery, Kevin Kalinsky, MD, of Columbia University in New York City, and colleagues reported.

The mean Ki-67 value did not change significantly in patients treated with metformin or among 58 similar patients who did not receive metformin prior to surgery. Treatment with metformin did lead to significant reductions in cholesterol (P<0.01) and leptin (P=0.03) and a trend toward reductions in insulin levels, HOMA, and adiponectin.

Results of a small Canadian study showed a consistent, potentially beneficial effect of metformin in women with early breast cancer. The study involved 39 nondiabetic women with newly diagnosed breast cancer. They received metformin for at least 2 weeks prior to diagnostic core biopsy.

Neoadjuvant metformin was associated with a significant (P<0.05) reduction in BMI, weight, glucose, and HOMA, and trend toward lower insulin levels. Ki-67 activity decreased significantly (P=0.0160), and TUNEL increased significantly (P=0.0037).

Insulin receptor expression decreased significantly (P=0.0375), as did AMPK (P=0.0034) and Akt signaling (P=0.0001), which are associated with tumor proliferation.

Taken together, the findings were consistent with beneficial anticancer effects of metformin, Ryan J.O. Dowling, PhD, of the Ontario Cancer Institute in Toronto, and colleagues reported. In particular, changes in insulin levels (as reflected in increased insulin receptor expression) and Akt signaling suggest metformin has clinically important insulin-dependent effects on tumor growth.

A second report based on the Canadian study delved into the details of biomarker analyses performed on tumor specimens. The primary objective was to gain clarifying mechanistic information to support metformin's anticancer activity.

The results were "compatible with the concept that metformin works in vivo via upregulation of tumor phosphorylated AMPK and down-regulation of phosporphylated Akt and proliferation," Sirwan M. Hadad, MD, of the University of Sheffield in England. "Since down-regulation of pAMPK is a feature of breast cancer, this suggests mechanistic evidence for the therapeutic effect of metformin."

The study by Pruneri and colleagues was supported by the Italian Association for Cancer Research (AIRC) and the Italian Ministry of Health.

The study by Dowling and colleagues was supported by the Banting Postdoctoral Fellowships program, Susan G. Komen for the Cure, and the Canadian Breast Cancer Foundation.

The study by Kalinsky and colleagues was supported by the Breast Cancer Research Foundation.

Pollak, Pruneri, Kalinsky, Dowling, and Hadad had no relevant disclosures.

 

 

Primary source: San Antonio Breast Cancer Symposium
Source reference:
Cazzaniga M, et al "The effect of metformn on apoptosis in a breast cancer presurgical trial" SABCS 2012; Abstract PD03-01.

Additional source: San Antonio Breast Cancer Symposium
Source reference:
Kalinsky K, et al "Presurgical trial of metformin in overweight and obese, multiethnic patients with newly diagosed breast cancer" SABCS 2012; Abstract PD03-03.

Additional source: San Antonio Breast Cancer Symposium
Source reference:
Dowling RJO, et al "Analysis of tumor cell signaling in response to neoadjuvant metformin in women with early-stage breast cancer" SABCS 2012; Abstract PD03-05.Amant F, et al "Breast cancer in pregnancy" Lancet 2012; 379: 570–79.

 

Additional source: The Lancet Oncology
Source reference:
Cardonick E "Treatment of maternal cancer and fetal development" Lancet Oncol 2012.

http://www.medpagetoday.com/MeetingCoverage/SABCS/36442

 

 

 

SIROD's picture
SIROD
Posts: 2116
Joined: Jun 2010

http://clinicaltrials.gov/show/NCT01101438

 

From the  Clinical Trials.gov  

A service of the U.S. National Institutes of Health

A Phase III Randomized Trial of Metformin vs Placebo in Early Stage Breast Cancer

This study is looking at whether Metformin, an agent that is commonly used to treat diabetes, can decrease or affect the ability of breast cancer cells to grow and whether Metformin will work with other therapies to keep cancer from recurring. Health Canada has not approved the sale or use of Metformin to treat breast cancer, although they have approved its use in this clinical trial. Although Metformin is approved by the FDA for the treatment of diabetes, its use in breast cancer is considered investigational.

 

Unhappy
Posts: 88
Joined: Dec 2012

I went to the site you put in here .It was helpful  Again thank youLaughing

burcu123
Posts: 70
Joined: Jan 2013

Fantastic review, must have taken a lot of time, very informative Thanks

CypressCynthia's picture
CypressCynthia
Posts: 3873
Joined: Oct 2009

I haven't heard anything about it but will research it.  Funny though, my sister was just mentioning that they are now using metformin with bipolar patients because it decreases insulin resistence and helps with weight gain that can both be caused by bipolar meds.

PennyJ's picture
PennyJ
Posts: 31
Joined: Dec 2012

as a treatment for ovarian cancer but hadn't heard about its use in breast cancer. 

burcu123
Posts: 70
Joined: Jan 2013

yes metformine has been shown to prevent and treat breast cancer.It is mainly used for ER and PR negative cancers. It is also preventive too. Diabetics who took metformine has 30% less chance of developing breast cancer.

 

Unhappy
Posts: 88
Joined: Dec 2012

to metformin the week before I found out I had cancer .Hoping that it does prove to be helpful in preventing it from coming  back.That would be good new since I have to take something for my blood sugar anyway

carlads's picture
carlads
Posts: 2
Joined: Dec 2012

I have also heard about Metfromin to help prevent recurrence.  I haven't talked to my Oncologist about it.  I was going to wait until after my Chemo is complete.

laughs_a_lot's picture
laughs_a_lot
Posts: 1368
Joined: Mar 2011

a lot of research on this in the last year or so.  I have not followed it closely.

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