Clinical and Biologic Effects of Metformin in Early Stage Breast Cancer

The study will be testing metformin in patients with breast cancer who are about to undergo surgery. Patients will take metformin 3 times daily for about 2-3 weeks prior to their surgery date. It is hypothesized that metformin will reduce cell proliferation rates in tumour tissue.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. invasive T1-4 (if T1, ≥ 1cm), NX operable breast cancer confirmed on core biopsy
2. < 70 years of age
3. breast surgery scheduled at least 2 weeks after study entry at one of the participating institutions (metformin will be started no more than 3 weeks prior to scheduled surgery) for the current breast cancer
4. patient and physician consent

Exclusion Criteria:

1. on metformin for any reason during the preceding 4 weeks
2. recent (within 4 weeks) antiestrogen or estrogen therapy
3. prior or concurrent systemic neoadjuvant BC therapy of any type (chemotherapy, hormone therapy, biologic therapy)
4. known diabetes or baseline fasting glucose > or = 7.0 mmol/L (specific treatment is required)
5. current or recent (within 4 weeks) use of drugs that may influence insulin or insulin sensitivity including oral corticosteroids, insulin sensitizers, exogenous insulin or oral hypoglycemic agents
6. serum creatinine above upper limit of normal for the institution
7. history of lactic or other metabolic acidosis
8. consumption of > 3 alcoholic beverages per day (on average)
9. AST > 1.5 times upper limit of normal for the institution
10. known hypersensitivity or allergy to metformin
11. current or past congestive heart failure
12. coagulopathy (including use of anti-coagulants) precluding biopsy
13. pregnancy or lactation within 3 months.

14. Serious psychiatric illness

    • Note: Women with childbearing potential will be required to use an effective form of birth control (condom or other barrier method, tubal ligation or vasectomy - oral contraceptives are contra-indicated in breast cancer) and to have a negative pregnancy test prior to starting metformin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin; Patients will take metformin three times a day for two to three weeks prior surgery.	Drug: Metformin; 500 mg tablet, taken 3 times a day for 2-3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine if taking metformin prior to surgery can reduce cell proliferation rates in tumour tissue. To be determined by tumour specimen analysis using pre- and post-operative biopsy sample.	two to three weeks

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada
• Collaborators: Princess Margaret Hospital, Canada

Publications and helpful links

General Publications

• Dowling RJ, Niraula S, Chang MC, Done SJ, Ennis M, McCready DR, Leong WL, Escallon JM, Reedijk M, Goodwin PJ, Stambolic V. Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res. 2015 Mar 3;17(1):32. doi: 10.1186/s13058-015-0540-0.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: May 8, 2009
• First Submitted That Met QC Criteria: May 8, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): January 19, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: breast cancer; metformin; breast surgery
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: METFORMIN