Metformin and Cancer Response

Targeting iron in cancer is ongoing.
This reduction of cancer in those with diabetes taking metformin gives
credence to the fact metformin may work by lowering body iron stores.
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Mascitelli L, Pezzetta F
Does metformin improve polycystic ovary syndrome symptoms through
reduction in body iron stores?
Eur J Endocrinol 2008 Mar; 158(3):439.
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Source: University of Texas M. D. Anderson Cancer Center
Released: Mon 02-Jun-2008, 13:50 ET

Metformin Increases Pathologic Complete Response Rates in Breast
Cancer Patients With Diabetes

METFORMIN, BREAST CANCER, DIABETES, M. D. ANDERSON CANCER CENTER,
ASCO, SAO JIRLERSPONG, M.D., PH.D., ANA M. GONZALEZ-ANGULO, M.D.
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Description

Metformin, the common first-line drug for type 2 diabetes, may be
effective in increasing pathologic complete response rates in diabetic
women with early stage breast cancer who took the drug during
chemotherapy prior to having surgery, paving the way for further
research of the drug as a potential cancer therapy, according to
researchers at The University of Texas M. D. Anderson Cancer Center.





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Ana M. Gonzalez-Angulo, M.D., assistant professor, in M. D. Anderson's
Department of Breast Medical Oncology.

Newswise — Metformin, the common first-line drug for type 2 diabetes,
may be effective in increasing pathologic complete response rates in
diabetic women with early stage breast cancer who took the drug during
chemotherapy prior to having surgery, paving the way for further
research of the drug as a potential cancer therapy, according to
researchers at The University of Texas M. D. Anderson Cancer Center.

The retrospective study is the first clinical research observation of
the diabetes drug as a potential anti-tumor agent. The findings will
be presented in a poster discussion session at the annual meeting at
the American Society of Clinical Oncology (ASCO) by Sao Jirlerspong,
M.D., Ph.D., a fellow, and Ana M. Gonzalez-Angulo, M.D., assistant
professor, both in M. D. Anderson's Department of Breast Medical
Oncology.

Metformin, an oral medication, is the most common drug prescribed for
type 2 diabetes; according to Gonzalez-Angulo, more than 35 million
prescription of the drug are filled annually. It's most often given to
diabetic patients who are obese or have insulin resistance.

The authors decided to conduct the research after a large, intriguing
epidemiologic study published last year showed that patients with
diabetes who took metformin had lower incidences of cancer as well as
better outcomes.

"Metformin has a novel mechanism of action. There have been a number
of papers published recently that describe its action through
activation of the AMP kinase pathway, which is a cellular energy
sensor of the cells and potentially important pathway for the
development of cancer," said Jiralerspong.

"The other interesting aspect is that Metformin works by decreasing
the amount of insulin- resistance in diabetics and insulin seems to be
a growth factor for cancer," said Gonzalez-Angulo.

Using the M. D. Anderson Breast Medical Oncology database, Gonzalez-
Angulo, Jiralerspong and their team identified 2,529 women with early-
stage breast cancer who received chemotherapy in the neoadjuvant
setting, before surgery. Of the patients, 2,374 were non-diabetic, 68
were diabetic but not taking metaformin and 87 were diabetic and
taking the drug. The study's endpoint was pathologic complete
response, or the absence of cancer at the time of surgery.

The researchers found that the pathologic complete response rates in
the diabetic breast cancer patients taking Metformin was 24 percent,
three times higher than the rates in diabetic patients not taking the
drug, 8 percent. In the non-diabetic women, the pathologic complete
response rate was 16 percent. After adjusting for other factors, the
researchers found that metformin was an independent predictor of
pathologic complete response in diabetic patients.

While very exciting, the findings are still very early, cautioned
Jiralerspong and Gonzalez-Angulo, and further investigation with
metformin is needed.

"We need to study the mechanism of the drug - perhaps it's the
decrease in insulin levels, or it may be that the drug has an anti-
tumor effect that we to look at in vivo," said Gonzalez-Angulo. "Our
next step is to conduct a number correlative studies to try and
further understand its mechanism."

M. D. Anderson also plans to open a clinical trial with metformin in
combination with hormonal therapy for metastatic breast cancer
patients who are obese. The study will be led by Francisco Esteva,
M.D., Ph.D., associate professor in the Department of Breast Medical
Oncology.

In addition to Gonzalez-Angulo and Jiralerspong, other authors of the
all-M. D. Anderson study include: Gabriel Hortobagyi, M.D., Mien Chie
Hung, Ph.D., Sharon Giordano, M.D., Funda Meric-Bernstam, M.D., Chad
Barnett and Shu-Wan Kau.

Updated data, including information about body mass index will be
presented 8 a.m. - noon on Mon., June 2 and will be discussed at 12:30
p.m. in a poster discussion session, "Breast Cancer - Local, Regional
and Adjuvant Therapy."

The University of Texas M. D. Anderson Cancer Center in Houston ranks
as one of the world's most respected centers focused on cancer patient
care, research, education and prevention. M. D. Anderson is one of
only 39 Comprehensive Cancer Centers designated by the National Cancer
Institute. For five of the past eight years, M. D. Anderson has ranked
No. 1 in cancer care in "America's Best Hospitals," a survey published
annually in U.S. News and World Report.

--------------------------------------------------------------------------------

© 2008 Newswise. All Rights Reserved


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