An Exploratory Study to Identify Potential Surrogate Endpoint Biomarkers That Are Modulated by Tamoxifen vs. Placebo in Women With an Increased Risk for Breast Cancer
35 Years
N/A
Female
Breast Cancer
Trial Information
An Exploratory Study to Identify Potential Surrogate Endpoint Biomarkers That Are Modulated by Tamoxifen vs. Placebo in Women With an Increased Risk for Breast Cancer
OBJECTIVES:
- Compare molecular markers of proliferation and apoptosis in breast epithelial tissue of
women at increased risk for breast cancer treated with tamoxifen vs placebo.
- Compare the modulation of markers of genomic instability in breast epithelial tissue of
patients treated with these drugs.
- Compare serum levels of IGF-1, IGF-2, and IGFBP-3 of these patients at baseline and
after treatment with these drugs.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to estimated 5-year breast cancer risk (1.67-5% vs ≥ 5%), presence
of atypical ductal hyperplasia (yes vs no), and menopausal status (premenopausal vs
postmenopausal). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral tamoxifen once daily.
- Arm I: Patients receive oral placebo once daily. Treatment in both arms continues for 3
months in the absence of invasive breast cancer or unacceptable toxicity.
Patients undergo core needle biopsy and fine needle aspiration biopsy at baseline and then
at the completion of study treatment (for premenopausal patients); exactly 84 days after the
first biopsy (for postmenopausal patients); or on the first or second day of the menstrual
cycle on or after 84 days (during the third menstrual cycle) after the first dose of study
medication (for patients with irregular menses).
Patients are followed at 30 days.
PROJECTED ACCRUAL: A total of 130 patients (65 per arm) will be accrued for this study
within 30 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- At increased risk for breast cancer, as defined by 1 of the following criteria:
- Histologically confirmed lobular carcinoma in situ (LCIS) treated by local
excision only
- Composite increased breast cancer risk of ≥ 1.67% over 5 years, based on the
following criteria:
- Age
- Number of first-degree female relatives with breast cancer
- One or more prior breast biopsies
- Fine-needle aspiration cytology of a non-cystic lesion in lieu of an
open biopsy is considered a biopsy
- Prior diagnosis of atypical hyperplasia of the breast
- Age at first live birth
- Nulliparity
- Race
- Age at onset of menarche
- No prior or suspected invasive breast cancer or ductal carcinoma in situ
- No clinical evidence of malignancy by physical examination, including a breast
examination within the past 3 months
- No evidence of suspicious or malignant disease or uncharacterized lesions on
bilateral mammogram within the past 6 months
- Normal gynecologic examination, including a bimanual pelvic examination and, if
indicated, pap smear within the past 12 months
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 35 and over
Sex
- Female
Menopausal status
- Premenopausal and ovulating*, defined as having regular menses for the past 6 months
OR irregular menses with follicular phase (i.e., day 3) follicle-stimulating hormone
level < 20 mIU/mL OR
- Postmenopausal NOTE: * Ovulation is determined by day 21 progesterone level > 3 ng/mL
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Complete blood count normal
- No active bleeding disorder (e.g., qualitative or quantitative platelet abnormality,
hemophilia, or von Willebrand's disease)
Hepatic
- Liver function tests normal
Renal
- Not specified
Cardiovascular
- No prior deep-vein thrombosis except a single occurrence related to lower extremity
trauma
- No prior cerebral vascular accident
- No prior transient ischemic attack
Pulmonary
- No prior pulmonary embolus except a single occurrence related to lower extremity
trauma
Other
- No saline or silicone breast implants
- No known allergy to tamoxifen
- No macular degeneration
- No malignancy within the past 5 years except basal cell or squamous cell skin cancer
or carcinoma in situ of the cervix
- No nonmalignant disease that would preclude administration of tamoxifen
- No psychiatric condition, including a history of clinical depression or addictive
disorder, that would preclude giving informed consent or study compliance
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective nonhormonal contraception during and for 3 months
after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior systemic adjuvant chemotherapy for LCIS
Endocrine therapy
- No prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators
- At least 3 months since prior and no concurrent use of any of the following drugs:
- Estrogen or progesterone replacement therapy
- Oral contraceptives
- Androgens
- Luteinizing hormone-releasing hormone analogs
- Prolactin inhibitors
- Antiandrogens
- Steroids
- No concurrent steroids for asthma
Radiotherapy
- No prior radiotherapy for LCIS
Surgery
- No prior bilateral prophylactic mastectomy
- No prior mastectomy for LCIS
Other
- Concurrent nonhormonal medications allowed
- No concurrent warfarin or cholestyramine
- No prior or concurrent participation in any other cancer prevention study
- Patients treated with placebo on protocol NSABP-P-1 are eligible
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Outcome Measure:
Plasma levels of hormones and binding proteins as measured by ELISA, IHC, and TUNEL at baseline and 3 months
Safety Issue:
No
Principal Investigator
David M. Euhus, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Simmons Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000393444
NCT ID:
NCT00096369
Start Date:
February 2002
Completion Date:
Related Keywords:
- Breast Cancer
- breast cancer
- lobular breast carcinoma in situ
- breast cancer in situ
- Breast Neoplasms
Name | Location |
|---|---|
| M.D. Anderson Cancer Center at University of Texas | Houston, Texas 77030 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| Cancer Therapy and Research Center | San Antonio, Texas 78229 |
