Trial Information

Protocol for Randomized Clinical Study Concerning Hormonal Replacement Therapy (HRT) After Previous Radical Breast Cancer Treatment

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.