Atorvastatin in Preventing Breast Cancer in Women at Increased Risk for Breast Cancer
Information source: M.D. Anderson Cancer Center
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer
Intervention: Atorvastatin (Drug)
Phase: Phase 1
Sponsored by: M.D. Anderson Cancer Center
Official(s) and/or principal investigator(s):
Banu Arun, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use
of atorvastatin (Lipitor) may prevent breast cancer.
PURPOSE: This randomized phase I trial is studying the best dose of atorvastatin in
preventing breast cancer in women at increased risk for breast cancer.
Official title: A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Changes in Ki-67
- 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 for developing breast cancer.
- To evaluate atorvastatin-induced modulation of breast cancer biomarkers (EGFR, P-EGFR,
ER, p21, p27, bcl-2, CC3, and cytology) and drug-related markers (LXR, total
cholesterol, LDL, HDL, CRP) in these participants.
- To determine plasma and tissue levels of atorvastatin and its hydroxylated metabolites
(o-hydroxyatorvastatin and p-hydroxyatorvastatin) and correlate these levels with Ki-67
- To correlate changes in Ki-67 and the above-described panel of biomarkers with HMG-CoA
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 biomarker studies.
Minimum age: 18 Years.
Maximum age: 72 Years.
1. Increased risk for breast cancer, defined by one of the following: - Greater than or
equal to 20% life long risk by Claus, Tyrer-Cuzick, BOADICEA, or BRCAPRO model, or a
5 year projected Gail risk of greater than or equal to 1. 67%; - Previous diagnosis of
lobular carcinoma in situ (LCIS) (per participating institution's pathology review),
or ductal carcinoma in situ (participants could have received any type of surgery and
radiation as long as they have an intact opposite breast).
2. Woman, age 18-72 years
3. The participant must have been properly informed of the study and must sign an
informed consent to be able to be enrolled in the study. The informed consent
document must be signed and dated prior to start of the study. No witnesses are
4. Normal physical exam, including a normal clinical breast examination, and mammogram
that shows no evidence of suspicious, malignant disease, or uncharacterized lesions
within last 12 months and no evidence of any active invasive cancer. (For abnormal
mammogram, if follow up tests such as ultrasound or biopsy shows no evidence of
suspicious, malignant disease, or uncharacterized lesions within last 12 months,
patients will be allowed on the study).
5. ECOG performance status = 1 (Karnofsky greater than or equal to 70%).
6. Participants must have normal organ and marrow function as defined below (up to 6
months prior to randomization): Leukocytes greater than 3,000/mL; Platelets greater
than 100,000/mL; Total bilirubin within normal institutional limits; AST (SGOT) /ALT
(SGPT) 1. 5 X institutional ULN; Creatinine within normal institutional upper limits;
CPK, PTT, PT within normal institutional upper limits (up to 1 month prior to
7. The effects of atorvastatin on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason, women of child-bearing potential must
agree to use adequate contraception (barrier method of birth control (IUD);
abstinence) prior to study entry and for the duration of study participation. Should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her study physician immediately.
8. If the participant is of childbearing potential, she must have a documented negative
urine pregnancy test within 14 days prior to randomization or start of the study
9. Normal bimanual pelvic examination within the last 12 months and any normal pap smear
within the last 3 years (or more often at the gynecologist's discretion) that show no
invasive cancer. Patients with total hysterectomy do not need to have pap smear.
1. Any type of active invasive cancer.
2. Bilateral mastectomy
3. Oral or injection use of contraceptives; androgens; luteinizing-hormone-releasing-
hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, tamoxifen, raloxifene,
or aromatase inhibitors. Women who discontinue these drugs at least 3 months prior to
study enrollment will be eligible.
4. Chronic medical condition that requires regular use of statins or steroids (unless
participants have discontinued these drugs 1 month prior to enrollment).
5. Participants may not be receiving any other investigational agents.
6. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to atorvastatin.
7. Uncontrolled psychiatric condition, including history of clinical depression, or
addictive disorder that would preclude obtaining informed consent or would interfere
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
9. Breast implantation
10. Pregnant women are excluded from this study because atorvastatin is a Class X agent
with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with atorvastatin breast feeding should be discontinued if
the mother is treated with atorvastatin.
Locations and Contacts
M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States; Recruiting
Clinical Trials Office - M. D. Anderson Cancer Center, Phone: 713-792-3245
Clinical trial summary from the National Cancer Institute's PDQ® database
UT MD Anderson Cancer Center website
Starting date: March 2008
Last updated: October 6, 2011