Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer

DISEASE CHARACTERISTICS:

• Estimated probability of carrying a BRCA1 or BRCA2 mutation ≥ 10% AND meets one of the following criteria:

  • Participants must have first-degree relatives (FDRs)* or second-degree relatives (SDRs)* (with an intervening male relative) with breast or ovarian cancer who satisfy one of the following criteria:

    • High-risk breast/ovarian cancer (non-Jewish families)

      • One FDR ≤ 40 years old** diagnosed with breast cancer
      • At least two FDRs or SDRs diagnosed with breast cancer at ≤ 50 years old OR had bilateral breast cancer
      • One FDR or one SDR diagnosed with breast cancer at ≤ 50 years old OR had bilateral breast cancer AND one FDR or SDR diagnosed with ovarian cancer
      • Three FDRs and/or SDRs diagnosed with breast or ovarian cancer (at least one in case of ovarian cancer)
      • Two FDRs and/or SDRs diagnosed with ovarian cancer
      • One male FDR or SDR diagnosed with breast cancer and one FDR or SDR (male or female) diagnosed with breast or ovarian cancer

    • Moderate-risk breast /ovarian cancer (non-Jewish families)

      • Two FDRs diagnosed with breast cancer with one ≤ 50 years old and/or both < 60 years old
      • One FDR and one SDR (mother or sister and maternal aunt or maternal grandmother) diagnosed with breast cancer if the sum of their ages is ≥ 118 years
      • One FDR and one SDR (mother or sister and paternal aunt or paternal grandmother) diagnosed with breast cancer if the sum of their ages is ≥ 78 years
      • Two SDRs (both maternal or both paternal) diagnosed with breast cancer if the sum of their ages is ≤ 98 years
      • One FDR with ovarian cancer

    • High-risk breast/ovarian cancer (Jewish families )

      • At least one FDR or SDR diagnosed with breast cancer at ≤ 50 years old
      • At least one FDR or SDR diagnosed with ovarian cancer
      • At least one FDR or SDR diagnosed with breast cancer at any age AND one FDR or SDR diagnosed with breast and/or ovarian cancer
      • At least one male FDR or SDR diagnosed with breast cancer NOTE: *FDRs are parents, siblings, and children of the participant; SDRs are aunts, uncles, grandparents, grandchildren, nieces, nephews, or half siblings of the participant

NOTE: **Age is approximated to the earliest age possible (e.g., a relative diagnosed in their 40's should be considered 40)

• Patterns of cancer cases must all be on the maternal or paternal side of the family

• Participants not meeting any of the above FDR or SDR criteria may provide medical documentation stating that they, a FDR, or a SDR carry BRCA1 or BRCA2 mutations

  • Participants with a prior history of breast cancer are eligible provided they have a remaining breast that has not been irradiated, all therapy for breast cancer was completed more than 2 years ago, and they are premenopausal
  • No ovarian cyst during screening
  • No more than 12 months since prior Pap smear with normal cytological results OR human papilloma virus negative if atypical squamous cells of uncertain significance (ASCUS) present

• No higher degrees of atypia beyond ASCUS on Pap smear

  • No known history of osteoporosis (bone mineral density > 1.5 standard deviations below young adult norms)
  • Hormone receptor status
• Not specified

PATIENT CHARACTERISTICS:

Menopausal status

• Premenopausal, as defined by 1 of the following:

  • Last menstrual period < 6 months ago
  • Less than 45 years old AND underwent partial hysterectomy OR follicle-stimulating hormone within institutional pre-menopausal range within the past 3 months

Sex

• Female

Performance status

• ECOG 0-1

Life expectancy

• More than 2 years

Hematopoietic

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 125,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST < 2 times upper limit of normal (ULN)
• Albumin ≥ 3.0 g/dL
• PT/PTT ≤ 1.25 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No history of deep venous thrombosis

Pulmonary

• No history of pulmonary embolism

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile participants must use effective barrier-method contraception during and for 3 months after completion of study treatment
• No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or cervical cancer ≤ stage I
• No known addiction
• Not undergoing treatment for an illicit drug addiction
• Willing and able to undergo required study procedures (e.g., research-related breast biopsies)

PRIOR CONCURRENT THERAPY:

Chemotherapy

• More than 2 years since prior chemotherapy

Endocrine Therapy

• At least 3 months since prior oral contraceptives or intramuscular progestational agent
• At least 3 months since prior luteinizing-hormone releasing hormone (LHRH) agonists or antagonists if agent was administered daily or monthly
• At least 6 months since prior LHRH agonists or antagonists if agent was administered every 3 months
• At least 6 months since prior antiestrogens (e.g., tamoxifen, toremifene, and raloxifene)
• No concurrent progestational or contraceptive agents

Radiotherapy

• See Disease Characteristics
• More than 2 years since prior radiotherapy

Surgery

• No prior prophylactic bilateral mastectomy

Other

• No concurrent cholestyramine
• No concurrent routine warfarin, bromocriptine, or phenobarbital
• No other concurrent investigational agents