Working… Menu

Tamoxifen in Preventing Breast Cancer in Women at Increased Risk for Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00096369
Recruitment Status : Terminated (accrual goal not met)
First Posted : November 9, 2004
Last Update Posted : January 24, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Brief Summary:

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of tamoxifen may be effective in preventing breast cancer.

PURPOSE: This randomized phase II trial is studying tamoxifen to see how well it works compared to placebo in preventing breast cancer in women who are at increased risk for the disease.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: tamoxifen citrate Phase 2

Detailed Description:


  • 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Masking: Double
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : February 2000
Actual Primary Completion Date : March 15, 2007
Actual Study Completion Date : March 15, 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Primary Outcome Measures :
  1. Plasma levels of hormones and binding proteins as measured by ELISA, IHC, and TUNEL at baseline and 3 months
  2. Markers of proliferation and apoptosis in breast cells as measured by quantitative MSP at baseline and 3 months
  3. Promoter-region methylation as assessed by microarrays at baseline and 3 months
  4. Gene expression

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   35 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • 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



  • 35 and over


  • 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


  • Complete blood count normal
  • No active bleeding disorder (e.g., qualitative or quantitative platelet abnormality, hemophilia, or von Willebrand's disease)


  • Liver function tests normal


  • Not specified


  • No prior deep-vein thrombosis except a single occurrence related to lower extremity trauma
  • No prior cerebral vascular accident
  • No prior transient ischemic attack


  • No prior pulmonary embolus except a single occurrence related to lower extremity trauma


  • 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


Biologic therapy

  • Not specified


  • 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


  • No prior radiotherapy for LCIS


  • No prior bilateral prophylactic mastectomy
  • No prior mastectomy for LCIS


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00096369

Layout table for location information
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Cancer Therapy and Research Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
University of Texas Southwestern Medical Center
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: David M. Euhus, MD Simmons Cancer Center
Layout table for additonal information
Responsible Party: University of Texas Southwestern Medical Center Identifier: NCT00096369    
Other Study ID Numbers: CDR0000393444; V-10604
First Posted: November 9, 2004    Key Record Dates
Last Update Posted: January 24, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by University of Texas Southwestern Medical Center:
breast cancer
lobular breast carcinoma in situ
breast cancer in situ
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents