None listed
Conditions
Brief summary
The aim of this study is to determine if we can prevent the development of uterine cancer in women who need to take tamoxifen therapy. 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 This study also offers a unique opportunity for us to determine whether all women with breast cancer should have ultrasound of their uterus before starting tamoxifen and after one year of therapy. 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 a 75% increase in the risk of uterine (endometrial) cancer. Presently there is no treatment to prevent endometrial cancer in women treated with tamoxifen, or for that matter for women in general. Endometrial cancer, the most common gynaecologic cancer, affects approximately 1 in 73 Australian women by the age of 75 years and 1 in 52 by the age of 85 years. We do know that: tamoxifen is associated with a 7 fold increase in endometrial cancer over 5 years most women who develop an endometrial abnormality on tamoxifen do so in the first year of treatment 1 in 5 women have an endometrial abnormality before starting tamoxifen (this increases the risk for tamoxifen-induced changes) We will recruit women with hormone receptor positive breast cancer who are postmenopausal, less than 75 years old not diabetic.
Interventions
Metformin 850mg oral twice daily for 12 months commencing with commencement of tamoxifen. Adherence will be monitored by return tablet count.
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
Postmenopausal women, aged < 75 years, who are currently taking tamoxifen therapy for at least 6 weeks for treatment of hormone receptor positive breast cancer.
Exclusion criteria
1. Women who are premenopausal / perimenopausal / > 75 years old 2. Women with advanced breast cancer and likely to have progression of their disease within the study period, as assessed by their treating oncologist. 3. Women with any of the following on screening: a)Use of any systemic hormones in the last 6 months; b) serious endocrine disorder with systemic disease; c) alcohol consumption greater than 3 standard drinks per day; d) known acute or chronic renal, liver disease or cardiovascular disease; e) insulin dependent diabetes mellitus or use of an oral hypoglycemic agent; 4. <6 months amenorrhoea so that the likelihood of ovulatory cycles during the study will be small. 5. EH with atypia or ECa on endometrial biopsy or hysteroscopy and curettage. 6. Women who, in the opinion of the investigator, are a poor medical or psychiatric risk for treatment in a research protocol.
Outcome results
None listed