RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. PURPOSE: Randomized double-blinded phase III trial to compare the effectiveness of tamoxifen with a placebo in preventing breast cancer in women at high risk.

OBJECTIVES: I. Evaluate whether tamoxifen taken daily for 5 years reduces the incidence of and mortality from breast cancer in high-risk women. II. Assess the risks and benefits of this intervention.

PROTOCOL OUTLINE: This is a randomized, double-blind, placebo-controlled study. Participants are stratified by participating institution. Participants are randomly assigned to receive either oral tamoxifen or oral placebo every day for 5 years in the absence of breast cancer development or pregnancy. Participants are followed every 6 months for 5 years; then annually for 5 years.

PROJECTED ACCRUAL: 7,000 women will be entered at a rate of 200-500 women/institution/5 years.

Ages Eligible for Study:  35 Years   -   70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Population Characteristics--

• Women with at least 1 risk factor for developing breast cancer, as follows: Ages 45-70 (with at least a 2-fold risk): First-degree relative developed breast cancer at age 50 or less; First-degree relative developed bilateral breast cancer 2 or more first- or second-degree relatives developed breast cancer; Nulliparous and a first-degree relative developed breast cancer; Benign biopsy with proliferative disease and a first-degree relative developed breast cancer; Lobular carcinoma in situ; Atypical ductal or lobular hyperplasia in a benign lesion
• Ages 40-44 (with at least a 4-fold risk) *: 2 or more first- or second-degree relatives developed breast cancer at age 50 or less; First-degree relative with bilateral breast cancer developed the first breast cancer at age 50 or less; Nulliparous and a first-degree relative developed breast cancer at age 40 or less; Benign biopsy with proliferative disease and a first-degree relative developed breast cancer at age 40 or less; Lobular carcinoma in situ; Atypical ductal or lobular hyperplasia in a benign lesion
• Ages 35-39 (with at least a 10-fold risk) *: 2 or more first-degree relatives developed breast cancer at age 50 or less; First-degree relative with bilateral breast cancer developed the first breast cancer at age 40 or less; Lobular carcinoma in situ
• Entry of women who do not fit into these categories but with a clearly apparent family history indicating appropriate risk requires approval of the Working Party Chairman
• No malignant disease on mammogram with, as indicated, fine-needle biopsy or cytology within 1 year prior to entry

--Prior/Concurrent Therapy--

• Hormone replacement therapy for menopausal symptoms allowed at lowest effective dose; Not currently on tamoxifen; Not currently on anticoagulants

--Patient Characteristics--

• Age: 35 to 70
• Sex: Women only
• Menopausal status: Pre-, peri-, or postmenopausal
• Performance status: Not specified
• Life expectancy: At least 10 years
• Cardiovascular: No prior deep vein thrombosis
• Pulmonary: No prior pulmonary embolus
• Other: Psychologically and physically able to undertake therapy for 5 years; No other medical condition more serious than risk of breast cancer; No prior cancer except: Nonmelanomatous skin cancer; In situ cancer of the cervix; No pregnant women; Effective nonhormonal contraception required of fertile women