Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer
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.
Biological: therapeutic estradiol
Drug: norethindrone acetate
|Study Design:||Allocation: Randomized
Masking: 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|
|Study Completion Date:||February 2004|
- 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.
|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|
|Stockholm, Sweden, S-171 76|
|Uppsala University Hospital|
|Uppsala, Sweden, S-75185|
|Zurich, Switzerland, CH-8008|
|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 Memorial Cancer Center, Institute of Oncology|