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: Randomizedphase 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	Treatment or Intervention	Phase
menopausal symptoms stage I breast cancer stage II breast cancer breast cancer in situ	Drug: estradiol  Drug: norethindrone  Procedure: adjuvant therapy  Procedure: endocrine therapy  Procedure: estrogen therapy  Procedure: hormone therapy  Procedure: menopausal symptoms attenuation  Procedure: replacement therapy  Procedure: supportive care/therapy	Phase III

Further Study Details: 

OBJECTIVES:

• 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.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age:

• Not specified

Sex:

• Female

Menopausal status:

• Menopausal or perimenopausal

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No active liver disease

Renal:

• Not specified

Cardiovascular:

• 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

Other:

• 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

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• 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

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

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

Finland
      Helsinki University Central Hospital, Helsinki,  FIN-00029,  Finland
Norway
      Norwegian Radium Hospital, Oslo,  N-0310,  Norway
Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland
Sweden
      Karolinska Hospital, Stockholm,  S-171 76,  Sweden
      Uppsala University Hospital, Uppsala,  S-75185,  Sweden
Switzerland
      Breast Center, Zurich,  CH-8008,  Switzerland

Study chairs or principal investigators

Lars Holmberg, MD, PhD,  Study Chair,  Uppsala University Hospital   
Jonas Bergh, MD, PhD,  Study Chair,  Karolinska Hospital   
C. Rageth, MD,  Study Chair,  Breast Center   
Janusz Jaskiewicz, MD,  Study Chair,  Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology   

Study ID Numbers:  CDR0000066897; ROC-HABITS; EORTC-10992; IBCSG-17-98; SBG-HABITS; EU-98077
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003771
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08