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Effect of 4-Hydroxytamoxifen Gel on Breast Density, Salivary Sex Steroids, and Quality of Life in Premenopausal Women

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: NCT00084344
Recruitment Status : Completed
First Posted : June 11, 2004
Last Update Posted : May 30, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Brief Summary:

RATIONALE: High estrogen levels may be associated with dense breast tissue and an increased risk of developing breast cancer. 4-hydroxytamoxifen gel (a substance made when tamoxifen breaks down in the body) may be effective in reducing breast density by reducing estrogen levels with fewer side effects than tamoxifen. This may improve quality of life and the ability to detect breast cancer with screening mammography.

PURPOSE: Randomized screening study to determine the effect of 4-hydroxytamoxifen gel on breast density, salivary sex steroids (hormones), and quality of life in premenopausal women.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: 4-hydroxytamoxifen Procedure: breast imaging study Procedure: radiomammography Not Applicable

Detailed Description:



  • Determine the effect of 4-hydroxytamoxifen gel on breast density, as measured by digital mammography, in premenopausal women.
  • Determine the effect of this gel on breast density in these participants, as defined by the BIRADS lexicon.


  • Determine the effect of this gel on salivary sex steroid levels in these participants.
  • Determine the effect of this gel on quality of life of these participants.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Participants are randomized to 1 of 2 treatment arms.

  • Arm I: Participants apply 4-hydroxytamoxifen gel in 4 metered doses daily to each breast beginning on the first day after cessation of the first menstrual period after digital mammography is performed.
  • Arm II: Participants apply placebo gel as in arm I. In both arms, treatment continues for 1 year.

In both arms, participants collect daily saliva samples for 4 menstrual cycles during the study. Three of the saliva collections occur during the cycles encompassing the time periods when imaging studies are performed (months 0, 6, and 12). The fourth collection takes place during the first month that gel is applied to the breast.

Participants also undergo digital mammography at baseline, 6 months, and 1 year.

Participants who develop clinical breast problems considered suspicious for cancer discontinue study treatment until a histological diagnosis is established. Those found to have breast cancer are removed from the study and those with benign disease continue the study. If an excisional biopsy is performed, density measurements are made on the opposite breast.

Quality of life is assessed at baseline, 1 month, 6 months, and 1 year.

PROJECTED ACCRUAL: A total of 100 participants (50 per treatment arm) will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Masking: Double
Primary Purpose: Screening
Official Title: A Prospective, Randomized, Placebo-Controlled Trial of the Effects of 4-Hydroxytamoxifen Gel on Breast Density, Salivary Sex Steroids, and Quality of Life in Premenopausal Women
Study Start Date : April 2003
Actual Primary Completion Date : July 2004
Actual Study Completion Date : July 2004

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes


  • Premenopausal as determined by a menstrual history of no change in menstrual pattern within the past 6 months
  • Undergoing mammography at least annually
  • No prior breast cancer
  • No clinical breast abnormalities suspicious for cancer
  • Hormone receptor status:

    • Not specified



  • 30 to 50


  • Female

Menopausal status

  • See Disease Characteristics

Performance status

  • Not specified

Life expectancy

  • Not specified


  • Not specified


  • Not specified


  • Not specified


  • Not pregnant or nursing
  • Fertile patients must use effective barrier contraception
  • No medical or psychiatric disorder that would preclude giving informed consent


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • More than 3 months since prior oral contraceptives or other estrogen- or progesterone-containing drugs
  • No prior tamoxifen for more than 1 month duration
  • No concurrent oral contraceptives or other estrogen- or progesterone-containing drugs
  • No other concurrent antiestrogen medications


  • Not specified


  • Not specified

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): NCT00084344

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United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
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Principal Investigator: Seema A. Khan, MD Robert H. Lurie Cancer Center
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Responsible Party: Northwestern University Identifier: NCT00084344    
Other Study ID Numbers: NCI 00B3
First Posted: June 11, 2004    Key Record Dates
Last Update Posted: May 30, 2012
Last Verified: May 2012
Keywords provided by Northwestern University:
breast cancer
Additional relevant MeSH terms:
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Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators