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Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage 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: NCT00003771
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : September 20, 2013
Scandinavian Breast Group
International Breast Cancer Study Group
European Organisation for Research and Treatment of Cancer - EORTC
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer.

PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms.

Condition or disease Intervention/treatment Phase
Breast Cancer Menopausal Symptoms Biological: therapeutic estradiol Drug: norethindrone acetate Phase 3

Detailed Description:


  • Evaluate the safety of hormone replacement therapy, in terms of risk of recurrence, in women with previously treated, nonrecurrent stage 0-II breast cancer.
  • Compare this regimen vs non-hormonal symptomatic treatment, in terms of quality of life and risk of death, in this patient population.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified by center, prior hormone replacement therapy before diagnosis, and concurrent tamoxifen therapy. Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive one of the following: Women with an intact uterus whose last menstrual bleeding has occurred within 2 years receive continuous oral cyclic estradiol-norethindrone combination comprising estradiol only on days 1-12, estradiol plus norethindrone on days 13-22, and then estradiol only on days 22-28. Women with an intact uterus whose last menstrual bleeding occurred more than 2 years prior to study receive continuous daily oral estradiol-norethindrone combination. Women who have had a hysterectomy receive continuous daily oral estradiol only.
  • Arm II: Patients receive one or more non-hormonal therapies (e.g., clonidine, beta blockers, psychological support, physical exercise, acupuncture).

Treatment in both arms continues for 2 years in the absence of disease progression. Patients may continue their randomized treatment regimen at the discretion of the treating physician.

Quality of life is assessed 3 times during the study and then every two years thereafter. Gynecological health is assessed at 3 months, 6 months, and one year during the study and then annually for at least 5 years. Breast cancer is assessed every 6 months for 3 years and then annually thereafter or at the discretion of the treating physician.

PROJECTED ACCRUAL: A total of 1,300 patients will be accrued for this study within 5-6 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1300 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Protocol for Randomized Clinical Study Concerning Hormonal Replacement Therapy (HRT) After Previous Radical Breast Cancer Treatment
Study Start Date : September 1997
Actual Study Completion Date : February 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:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • History of stage 0-II breast cancer with no more than 4 involved axillary nodes if nodal status and number of nodes investigated is known
  • No current evidence of disease
  • Hormone receptor status:

    • Positive, negative, or unknown



  • Not specified


  • Female

Menopausal status:

  • Menopausal or perimenopausal

Performance status:

  • Not specified

Life expectancy:

  • Not specified


  • Not specified


  • No active liver disease


  • Not specified


  • No prior or concurrent deep vein thrombosis
  • No hereditary traits for deep vein thrombosis
  • No prior or concurrent cerebral stroke
  • No prior or concurrent coronary disease


  • No prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
  • No porphyria
  • No other serious disease that would prevent compliance or greatly limit life expectancy


Biologic therapy:

  • Not specified


  • No concurrent chemotherapy

Endocrine therapy:

  • Prior hormone replacement therapy (HRT) allowed if stopped no more than 4 weeks after breast cancer diagnosis and at least 3 months prior to study
  • No prior HRT initiated after breast cancer diagnosis
  • No concurrent hormonal therapy for breast cancer except tamoxifen or toremifene


  • No concurrent radiotherapy


  • Not specified


  • No prior randomization into trials comparing effects of chemotherapy and bilateral oophorectomy in premenopausal women

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): NCT00003771

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Helsinki University Central Hospital
Helsinki, Finland, FIN-00029
Norwegian Radium Hospital
Oslo, Norway, N-0310
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Warsaw, Poland, 02-781
Karolinska Hospital
Stockholm, Sweden, S-171 76
Uppsala University Hospital
Uppsala, Sweden, S-75185
Breast Center
Zurich, Switzerland, CH-8008
Sponsors and Collaborators
Regional Oncologic Center
Scandinavian Breast Group
International Breast Cancer Study Group
European Organisation for Research and Treatment of Cancer - EORTC
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Study Chair: Lars Holmberg, MD, PhD Uppsala University Hospital
Study Chair: Jonas Bergh, MD, PhD Karolinska Institutet
Study Chair: C. Rageth, MD, PD Breast Center
Study Chair: Janusz Jaskiewicz, MD Maria Sklodowska-Curie National Research Institute of Oncology
Publications of Results:
Other Publications:
Layout table for additonal information Identifier: NCT00003771    
Other Study ID Numbers: CDR0000066897
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: September 20, 2013
Last Verified: July 2001
Keywords provided by National Cancer Institute (NCI):
menopausal symptoms
stage I breast cancer
stage II breast cancer
breast cancer in situ
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Norethindrone Acetate
Polyestradiol phosphate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents, Hormonal
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Contraceptives, Oral, Hormonal
Contraceptives, Oral
Contraceptives, Oral, Synthetic