Breast Cancer & Metformin (Glucophage)

doctorwascher

Breast Cancer & Metformin (Glucophage)

Patients with diabetes are thought to be at increased risk of developing certain types of cancer, as well as being at an increased risk of developing a recurrence of previously diagnosed cancers.  For example, an increased risk of recurrent breast cancer has, specifically, been linked to obesity and diabetes in women.  Among other possible explanations, elevated levels of insulin are thought to act as a stimulus for cancer cells to grow and divide.  Other diabetes-associated molecules also appear to cause increased cancer cell proliferation, or growth, including insulin-like growth factor (IGF).

Metformin, also known as Glucophage, has become the most commonly prescribed oral medication for the treatment of diabetes.  Previous laboratory and public health studies have suggested that metformin may also be able to suppress cancer cell proliferation, and to reduce the risk of death due to cancer.  However, thus far, there has been very little direct clinical research evidence available to support this hypothesis.

A new clinical research study, just published in the Journal of Clinical Oncology, sheds further light on the potential role of metformin as a possible new treatment for breast cancer.  In this retrospective clinical study from the M.D. Anderson Cancer Center, the medical records of 2,529 patients who received chemotherapy as initial treatment (neoadjuvant chemotherapy) for their early stage breast cancers, between 1990 and 2007, were reviewed.   This group of breast cancer patients included 68 diabetic patients who were taking metformin, 87 diabetic patients who were not taking metformin, and 2,374 nondiabetic patients.  All 2,529 patients subsequently went on to have surgery for their breast cancers, and the researchers then assessed the response of each woman's breast cancer to their initial chemotherapy.

A pathological complete response to chemotherapy occurs when the pathologist can no longer find any evidence of residual cancer after surgical removal of the original cancer site.  (In general, a pathological complete response to neoadjuvant chemotherapy is associated with a better prognosis.)  The incidence of pathological complete response to neoadjuvant chemotherapy was then evaluated in each of the three groups of women involved in this clinical study.

In this study, the diabetic women who were taking metformin were found to have three times the rate of pathological complete response to neoadjuvant chemotherapy when compared to the diabetic women who were not taking metformin (there was no statistically significant difference between the diabetic women taking metformin and the nondiabetic women, although there was still a trend towards improved pathological complete response in the metformin group). 

While the retrospective nature of this study, and the relatively small numbers of diabetic women included in the study, significantly limits the conclusions that can be drawn, these results are consistent with other previous research findings.  Taken together, this data strongly suggests that metformin may be able to, at a minimum, counteract the proliferative effects of diabetes on breast cancer cells.  This finding raises the question as to whether or not diabetic women who are diagnosed with breast cancer should be routinely placed on metformin as part of their overall cancer treatment program.  Since this clinical study also detected a non-significant improvement in pathological complete response rates among diabetic women taking metformin, when compared to nondiabetic women, larger prospective clinical research studies may also help us to understand whether or not metformin might be clinically useful in treating breast cancer in women who do not have diabetes, as well.

Currently, there are several prospective clinical research trials underway, looking at the role of metformin in the management of breast cancer (and at least one such clinical trial for prostate cancer, as well).  Hopefully, one or more of these prospective clinical research trials will help us to better understand the role, if any, for metformin as a potential breast cancer therapy in diabetic women (and, perhaps, in nondiabetic women as well).  Meanwhile, if you are a breast cancer survivor with diabetes, and you are not taking metformin, you might be well advised to discuss this data with your Oncologist.

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Disclaimer:  As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity

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Dr. Wascher is an oncologic surgeon, a professor of surgery, a widely published author, and a Surgical Oncologist at the Kaiser Permanente healthcare system in Orange County, California

http://doctorwascher.com

orange1

Thanks for posting.  Interesting article.  I like your website too.

anondenet

Drwasscher wrote:

In this study, the diabetic women who were taking metformin were found to have three times the rate of pathological complete response to neoadjuvant chemotherapy when compared to the diabetic women who were not taking metformin (there was no statistically significant difference between the diabetic women taking metformin and the nondiabetic women, although there was still a trend towards improved pathological complete response in the metformin group). "

This is a bit of a bombshell. It suggests carb control as a nontoxic, possible lifelong adjuvant therapy?

Need to read more on this!

orange1

Perhaps it has something to do with IGF (insulin-like growth factor) that was been discussed in the literature lately.  

I have been planning to get a glucose meter (even though I am not diabetic) so see which foods/eating habits elevate my blood glucose level more sharply.  Kind of do a little experiment on myself.  Unfortunately, then I will have one more thing to feel guilty about if I persist in eating foods that in raise it, with no hard evidense that it will affect chance of recurrence.  But on the other hand, maybe it will help me keep my weight down.

Background info from Pfizer website:

IGF-1R is an IGF receptor. 

The IGF-1R Signaling Pathway in Cancer
The IGF-1R promotes tumor growth and evasion from apoptosis

Evidence from preclinical and clinical studies suggests that signaling through IGF-1R-mediated pathways regulates multiple processes of cancer initiation, progression, and in some instances, resistance to therapy.^1-3 Tumor cells appear to rely on the IGF-1R signaling pathway as a pro-survival and anti-apoptotic mechanism that¹:

• Facilitates malignant transformation^1-3
• Causes growth and progression of established tumors^1-3
• Enhances tumor invasion and metastasis^1-3
• Contributes to resistance to therapy by providing an escape pathway for tumor cells²

IGF-1R signaling may play a role in multiple tumor types

Signaling through IGF-1R has been implicated in lung cancer.

• Elevated plasma levels of IGF-1 were associated with an increased risk of lung cancer¹
• IGF-1, IGF-2, and IGF-1R are expressed in normal lung cells and overexpressed in lung cancer cells^6,7

IGF-1R signaling has also been implicated in breast cancer, prostate cancer, colorectal cancer, sarcoma, multiple myeloma, and other malignancies.^2,3

IGF-1R Is Being Investigated as a Target in Cancer Research
Antitumor activity is observed with selective inhibition of IGF-1R

Preclinical data from studies of multiple tumor types suggest that the IGF-1R signaling pathway should be investigated as a target in cancer research.^1,2

• Selective IGF-1R inhibition may result in:
  • Apoptosis of tumor cells²
  • Inhibition of tumor formation²
  • Inhibition of tumor metastasis³

Information in the Oncology Investigational Pipeline relates to therapies currently being researched.

References: 1. Ryan PD, Goss PE. The emerging role of insulin-like growth factor pathway as a therapeutic target in cancer. Oncologist. 2008;13:16-24. 2. Hartog H, Wesseling J, Boezen HM, van der Graff WTA. The insulin-like growth factor 1 receptor in cancer: old focus, new future. Euro J Cancer. 2007;43:1895-1904. 3. Sachdev D, Yee D. Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther. 2007;6:1-12. 4. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocrine Rev. 2007;28:20-47. 5. Cosaceanu D, Carapancea M, Alexandru O, et al. Comparison of three approaches for inhibiting insulin-like growth factor 1 receptor and their effects on NSCLC cell lines in vitro. Growth Factors. 2007;25:1-8. 6. Kaiser U, Schardt C, Brandscheidt D, Wollmer E, Havemann K. Expression of insulin-like growth factor 1 receptors I and II in normal human lung and in lung cancer. J Cancer Res Clin Oncol. 1993;119:665-668. 7. Quinn KA, Treston AM, Unsworth EJ, et al. Insulin-like growth factor expression in human cancer cell lines. J Biol Chem. 1996;271:11477-11483.