Breast Cancer
Conditions
Keywords
Breast Cancer, Metformin
Brief summary
The purpose of this pilot study is to use a pre surgical intervention model to evaluate the biologic effects of metformin in women with newly diagnosed early invasive breast cancer. Metformin is a drug commonly used to treat patients with diabetes. This model will be used to evaluate the effects of metformin.
Detailed description
Breast cancer is the most common cancer and the second leading cause of cancer death among women in the United States. Several epidemiologic studies have found an increased risk of breast cancer in women with type 2 diabetes. This association appears to be mediated by a state of hyperinsulinemia and insulin resistance. Population based studies have also found a decreased risk of cancer in diabetic patients taking metformin, an oral biguanide derivative. Proposed mechanisms include its effect on lowering serum insulin levels as well as modulation of cellular signaling pathways which inhibit tumor cellular proliferation.
Interventions
DRUGMetformin
1500 mg per day, divided 500 mg in the morning and 1000 mg in the evening, for at least two weeks prior to surgery
Sponsors
Breast Cancer Research Foundation
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed operable invasive breast cancer or ductal carcinoma in situ (DCIS) who undergo core needle biopsy followed by surgical excision at least 2 weeks after enrollment * Body mass index \> 25 * Age ≥ 21 years * No prior chemotherapy, radiation therapy, or surgery within 6 months of study entry * Signed informed consent
Exclusion criteria
* History of diabetes mellitus requiring medical therapy * Treatment with other investigational drugs within 6 months of study entry * Significant renal impairment with a creatinine \> 1.4 mg/dl * Other serious intercurrent medical illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Proliferation in Tumor Specimens | Baseline, up to 4 weeks | This outcome measure examines the changes in tumor proliferation as measured by the amount of Ki-67 protein in the tumor. |
Countries
United States
Participant flow
Recruitment details
The investigator conducted an open-label, single-arm, presurgical trial with metformin at Columbia University Medical Center (CUMC) in New York, New York. Between October 2009 and August 2011.
Participants by arm
| Arm | Count |
|---|---|
| Metformin Women with newly diagnosed early invasive breast cancer received doses of the study drug, Metformin, for at least two weeks before their scheduled surgery. Participants received 1500mg of metformin per day- 500mg in the morning, and 1000mg in the evening. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Discontinued due to rescheduled surgery | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Metformin |
|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 11 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 28 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 2 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 2 Participants |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 33 |
| other Total, other adverse events | 29 / 33 |
| serious Total, serious adverse events | 0 / 33 |
Outcome results
Primary
Tumor Proliferation in Tumor Specimens
This outcome measure examines the changes in tumor proliferation as measured by the amount of Ki-67 protein in the tumor.
Time frame: Baseline, up to 4 weeks
Population: Of the evaluable metformin-treated patients, 33 participants were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin | Tumor Proliferation in Tumor Specimens | Premetformin Tumor Sample | 2.17 percentage of ki-67 positive cells | Standard Deviation 1.6 |
| Metformin | Tumor Proliferation in Tumor Specimens | Post Metformin Tumor Sample | 2.165 percentage of ki-67 positive cells | Standard Deviation 1.67 |
Comparison: Null hypothesis: there will be no statistically significant change between the amount of Ki-67 (protein involved in cell proliferation) in participants' tumor cells before and after taking the prescribed dose of Metformin, as measured at the 5% significance level.p-value: 0.98paired t-test