A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer
I. To determine the minimum biological effective dose (MBED) of atorvastatin required to
induce modulation in the proliferation marker, Ki-67, in breast tissue of women who are at
high risk to develop breast cancer. We will evaluate pre- and post atorvastatin treatment (4
dose levels) expression of Ki-67 in samples obtained via FNA from breast tissue of women at
high risk for breast cancer. This specific aim tests the hypothesis that treatment with
atorvastatin will induce a decrease in Ki-67.
I. To evaluate atorvastatin induced modulation of breast cancer biomarkers markers (EGFR,
P-EGFR, ER, p21, p27, bcl-2, CC3, cytology) and drug related markers (LXR, total
cholesterol, LDL, HDL, CRP) in women who are at high risk to develop breast cancer.
II. To determine plasma and tissue levels of atorvastatin and two of its hydroxylated
metabolites (ohydroxyatorvastatin and p-hydroxyatorvastatin) in women who are treated with
atorvastatin and to correlate these levels with Ki-67 levels. III. To correlate changes in
Ki-67 and the above-described panel of biomarkers with HMG-CoA reductase genotype.
OUTLINE: Participants are randomized to 1 of 4 arms.
ARM I: Participants receive oral atorvastatin once daily for 3 months.
ARM II: Participants receive oral atorvastatin (at a higher dose than in arm I) once daily
for 3 months.
ARM III: Participants receive oral atorvastatin (at a higher dose than in arm II) once daily
for 3 months.
ARM IV: Participants do not receive treatment. Participants undergo blood sample collection
and fine needle aspiration of breast tissue at baseline and at 3 months for correlative
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Atorvastatin induced changes in proliferation rate measured by Ki-67
A single proliferation rate at each time period is calculated for each participant based on the proportion cells expressing KI-67.
Baseline to 3 months
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M D Anderson Cancer Center||Houston, Texas 77030|