Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer
Protocol for Randomized Clinical Study Concerning Hormonal Replacement Therapy (HRT) After Previous Radical Breast Cancer Treatment
  • Phase

    Phase 3
  • Study Type

  • Status

    Completed No Results Posted
  • Study Participants

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.

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.
Study Started
Sep 30
Study Completion
Feb 29
Last Update
Sep 20

Biological therapeutic estradiol

Drug norethindrone acetate



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



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
No Results Posted