Investigating Prevention of Endometrial Cancer with Metformin (PECAM Study)

Chief Investigators

  • Professor Susan Davis, School of Public Health and Preventive Medicine, Monash University
  • Professor Robin Bell, School of Public Health and Preventive Medicine, Monash University
  • Dr Kristy Brown, Prince Henry's Institute of Medical Research

Key Associate Investigators

Drs: Shane White, Mitchell Chipman, Jillian Woinarski, Jane McNeilage, Sofie Piessens, Andrew Edwards

Aim

The aim of this study is to determine if we can prevent the development of uterine changes in women who need to take tamoxifen therapy.

Metformin is a medication used to treat diabetes. Metformin also appears to have important anti-cancer effects and is currently being investigated as part of the treatment of breast cancer. There is evidence to suggest that metformin might protect the lining of the uterus from changes that might progress to uterine cancer.

We will investigate whether metformin, commonly used to treat diabetes, blocks cell pathways by which tamoxifen (and oestrogen) stimulates growth of the lining of the uterus.

This study will enable us to determine if there is a potential role for metformin a) to prevent changes to the uterine lining in women treated with tamoxifen b) possibly prevent cancer of the uterus.

Reasons for the study

Over 75% of women diagnosed with breast cancer in Australia have hormone sensitive cancer. Of these, at least 1/3 will be treated with a drug called tamoxifen, which blocks oestrogen action. A recent large study has shown that 10 years of tamoxifen therapy is more effective than 5 years in prolonging survival.
However, a downside of tamoxifen therapy is an estrogen-like effect on the lining of the uterus which can result in thickening of the lining of the uterus and changes that precede the development of uterine (endometrial) cancer.

Presently there is no treatment to block these effects of tamoxifen. There is also no treatment to prevent uterine cancer in women in the community. As uterine cancer, is the most common gynaecologic cancer in women (1 in 73 Australian women by the age of 75 years) identification of a way to prevent uterine cancer in at risk women is important.

For this study we will recruit women with hormone receptor positive breast cancer who are:

  • postmenopausal
  • less than 75 years old
  • not diabetic

Benefits for participants include:

1. Having a transvaginal ultrasound done by an expert gynaecologist at no cost before and after 12 months of treatment.
2. Having your glucose and insulin (diabetes risk) monitored before and after 12 months of treatment.
3. Having a 50% chance of being treated with metformin, at a dose that is being tested in other studies to treat breast cancer.

If you participate in this study you will take your tamoxifen as prescribed with either study drug (metformin) or identical placebo, for 1 year.

You will be asked to have a transvaginal ultrasound, done by an expert gynaecologist to assess the lining of your uterus (at no cost to you).

If the lining is thin (less than 4mm) you will then start study medication. If the lining is thickened (4mm or more) or abnormal, we will arrange for an endometrial sample to be taken by an expert gynaecologist, at no cost to you.

At study's end we will repeat the ultrasound and, if indicated, the biopsy.

Participants will be seen at the Women's Health Research Program at the Alfred Centre (Alfred Hospital) Melbourne, but will stay under the care of their own breast cancer doctors through the study.

Recruitment is closed.

For enquiries call: Corallee Morrow + 61 3 9903 0836 or Ashley Baring + 61 3 9903 0830, or email med-pecam@monash.edu at the Women's Health Research Program, Monash University.

This study is funded by the National Health and Medical Research Council of Australia (Chief Investigator, Professor Susan Davis; Grant No 1061800) and has the support of the Breast Cancer Network of Australia.