This randomized phase III trial studies metformin hydrochloride to see how well it works compared to placebo in preventing breast cancer in patients with atypical hyperplasia or in situ breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of metformin hydrochloride may prevent breast cancer.
I. Test for the presence or absence of cytological atypia (as measured by a Masood Cytology Index Score of 14-17) in unilateral or bilateral random periareolar fine needle aspiration (RPFNA) aspirates after 12 and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin \[metformin hydrochloride\]) for women receiving metformin versus placebo control. The presence of cytological atypia means any atypia in any RPFNA specimen. SECONDARY OBJECTIVES: I. Use the Masood Cytology Index Score to test for the presence of cytological atypia or disappearance of cytological atypia in RPFNA aspirates after 12 months for both arms, and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin, and mandatory for crossover patients) for women receiving metformin 850 mg orally (PO) twice daily (BID) (metformin group). II. Compare Masood Cytology Score values at 0 and 12 months in right and left breasts (if both breasts were aspirated) from the same individual in the metformin and placebo group. III. Test the reproducibility of reverse phase protein microarray (RPPM) in duplicate RPPM determinations from individual RPFNA specimens. IV. Correlate baseline RPPM values with presence of atypia (as measured by Masood Cytology Index Score) at month 12 and month 24 (month 24 optional for placebo-only group; for patients who remain on placebo arm and will not receive metformin) RPFNA. TERTIARY OBJECTIVES: I. Test whether metformin alters RPFNA or blood biomarkers associated with breast cancer risk. II. Test whether metformin alters markers associated with obesity and insulin resistance. III. Test other exploratory measures in RPFNA and serum including metformin levels and estrogen/progesterone. IV. Banking: As part of ongoing research for Alliance Cancer Control studies, banking residual blood and RPFNA products for future studies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
86
given PO
given PO
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Los Angeles County-USC Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
The Community Hospital
Munster, Indiana, United States
Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months.
Presence of atypia at 12 months is determined through the average of Masood scores across all evaluable breasts for a patient. If the average score is at least 13.5, then patient will be labeled as having atypia. The primary aim of this study is to compare the presence of atypia at month 12 between two arms using the chi-square test in univariable analysis and regressed on group indicator, age, race, stratification factors, and baseline Masood score using logistic regression in multivariable analysis.
Time frame: 12 months
Test for the Masood Score and the Presence of Atypia or Disapperance of Atypia in RPFNA After 12 Months (for Both Arms) and 24 Months for Metformin Arm.
Time frame: Up to 24 months
Compare Masood Cytology Score Value at 0 and 12 in Right and Left Breast From the Same Individual in the Metformin and Non-metformin Group.
Time frame: Up to 24 months
Test the Reproducibility of RPPM in Duplicate RPPM Determinations From Individual RPFNA Specimens.
Time frame: Up to 12 months
Correlate Baseline RPPM Values With Presence of Atypia at Month 12 and Month 24.
Time frame: Up to 24 months
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Kansas City, Kansas, United States
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...and 17 more locations