Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer in Postmenopausal Women

Study Overview
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Brief Summary
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using raloxifene and tamoxifen may fight breast cancer by blocking the uptake of estrogen by the tumor cells. PURPOSE: Randomized double-blinded clinical trial to compare the effectiveness of raloxifene with that of tamoxifen in preventing breast cancer in postmenopausal women.

Detailed Description
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OBJECTIVES: Determine whether raloxifene is more or less effective than tamoxifen in significantly reducing the incidence rate of invasive breast cancer in postmenopausal women. Evaluate the effects of tamoxifen and raloxifene on the incidence of intraductal carcinoma in situ, lobular carcinoma in situ, endometrial cancer, ischemic heart disease, fractures of the hip and spine, or Colles' fractures of the wrist in these participants. Evaluate the toxic effects of these regimens in these participants. Determine the effect of these regimens on the quality of life of these participants (at selected centers). (Quality of life evaluation closed to accrual effective 5/31/01.) OUTLINE: This is a randomized, double-blind study. Participants are stratified by age (35 to 49 vs 50 to 59 vs over 59), race (black vs white vs other), history of lobular carcinoma in situ (yes vs no), prior hysterectomy (yes vs no), and estimated absolute risk of invasive breast cancer within 5 years (using the Gail model)(less than 2.0 vs 2.0-2.9 vs 3.0-4.9 vs 5.0 or greater). Participants are randomized to 1 of 2 arms. Arm I: Participants receive oral tamoxifen plus placebo daily for 5 years. Arm II: Participants receive oral raloxifene plus placebo daily for 5 years. Quality of life is assessed (at selected centers) at baseline and at 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 72 months. (Quality of life evaluation closed to accrual effective 5/31/01.) Participants are followed annually after 5 years. PROJECTED ACCRUAL: Approximately 19,000 participants will be accrued for this study within 5 years.

Official Title
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Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Raloxifene
* Drug: Tamoxifen


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Postmenopausal women at increased risk for developing invasive breast cancer, who meet one of the following criteria: At least 12 months since spontaneous menstrual bleeding Prior documented hysterectomy and bilateral salpingo-oophorectomy At least 55 years of age with prior hysterectomy with or without oophorectomy Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of ovaries unknown with documented follicle-stimulating hormone level demonstrating elevation in postmenopausal range Histologically confirmed lobular carcinoma in situ treated by local excision only OR a minimum projected 5 year probability of invasive breast cancer of at least 1.66%, using Breast Cancer Risk Assessment Profile No clinical evidence of malignancy on physical exam within the past 180 days No evidence of suspicious or malignant disease on bilateral mammogram within the past year No bilateral or unilateral prophylactic mastectomy No prior invasive breast cancer or intraductal carcinoma in situ Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 35 and over Sex: Female Menopausal status: See Disease Characteristics Performance status: No restricted normal activity for a significant portion of each day Life expectancy: At least 10 years Hematopoietic: Granulocyte count at least 1,500/mm^3 Complete blood count and differential normal Platelet count normal Hepatic: SGOT or SGPT normal Bilirubin normal Alkaline phosphatase normal Renal: Creatinine normal Cardiovascular: No cerebral vascular accident, transient ischemic attack, atrial fibrillation, or uncontrolled hypertension No deep vein thrombosis Pulmonary: No pulmonary embolus Other: No other prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No concurrent nonmalignant disease that would preclude administration of tamoxifen or raloxifene No clinical depression, psychiatric condition, or addictive disorder No uncontrolled diabetes PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: At least 3 months since prior estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin inhibitors, or antiandrogens At least 3 months since prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators of less than 3 months duration Concurrent Estring allowed Radiotherapy: No prior breast radiotherapy Surgery: See Disease Characteristics Other: No prior systemic adjuvant therapy for breast cancer No other participation in a cancer prevention or osteoporosis prevention study involving pharmacologic intervention(s) NSABP-P-1 patients who received placebo are eligible No concurrent warfarin or cholestyramine Concurrent calcitonin or nonhormonal medication (e.g., cholecalciferol, fluoride, or bisphosphonates) allowed

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Tamoxifen and placebo | Drug: Tamoxifen<br>* 20 mg/day plus placebo for 5 years<br>|
| Experimental: Group 2<br>Raloxifene and Placebo | Drug: Raloxifene<br>* 60 mg/day plus placebo for 5 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of invasive breast cancer; superiority of one of the therapies. | Determine which of the following is true: compared to tamoxifen, raloxifene significantly reduces the incidence rate of invasive breast cancer; compared to raloxifene, tamoxifen significantly reduces the incidence rate of invasive breast cancer; or the statistical superiority of one of the treatments cannot be demonstrated and the choice of therapy should be based on benefit/risk considerations. | Time from randomization to the occurance of invasive breast cancer. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of the study therapies on the incidence of intraductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS). |  | Time from randomization to the occurance of DCIS or LCIS. | 
| Effect of the study therapies on the incidence of endometrial cancer. |  | Time from randomization to the occurance of endometrial cancer. | 
| Effect of the study therapies on the incidence of ischemic heart disease. |  | Time from randomization to the occurance of ischimic heart disease. | 
| Effect of the study therapies on the incidence of fractures of the hip, spine, or Colles' fractures of the wrist. |  | Time from randomization to the occurance of fractures of the hip, spine, or Colles' fractures of the wrist. | 
| Effect of the study therapies on the toxicity and side effects of each therapy. |  | Incidences of protocol defined toxicities and side effects. | 
| Effect of the study therapies on participants' quality of life. |  | pre-entry, every 6 months for 5 years, and then annual after 5 years following randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer