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

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.

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