IH636 Grape Seed Extract in Preventing Breast Cancer in Postmenopausal Women at Risk of Developing Breast Cancer

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of IH636 grape seed extract may prevent breast cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of IH636 grape seed extract in preventing breast cancer in postmenopausal women at risk of developing breast cancer.

OBJECTIVES:

• Determine the efficacy of IH636 grape seed proanthocyanidin extract, in terms of suppression of estrogen biosynthesis, in healthy post-menopausal women at high risk of developing breast cancer.
• Determine the safety and tolerability of this dietary supplement, in terms of symptoms and changes in markers of bone metabolism and in markers of nonspecific adrenal suppression, in these participants.
• Determine, preliminarily, an optimum biologic dose of this dietary supplement, as defined by suppression of serum estradiol, in these participants.
• Determine a suggested dose of this dietary supplement for aromatase inhibition in these participants.

OUTLINE: This is a pilot, dose-finding, placebo-controlled study.

Participants receive oral placebo once or twice daily on days -14 to 0. Participants then receive oral IH636 grape seed proanthocyanidin extract once or twice daily on days 1-85. Treatment continues in the absence of toxicity.

Cohorts of 6 participants receive escalating doses of IH636 grape seed proanthocyanidin extract up to an established safe dose.

PROJECTED ACCRUAL: A total of 24 participants will be accrued for this study within 12 months.

Accepts Healthy Volunteers

DISEASE CHARACTERISTICS:

• At increased risk of developing breast cancer, as defined by 1 of the following risk factors:
• Gail model 5-year risk ≥ 1.67%
• Gail or Claus model lifetime risk ≥ 15%
• No prior history of breast cancer or ductal carcinoma in situ

PATIENT CHARACTERISTICS:

Age

• 50 to 65

Sex

• Female

Menopausal status

• Postmenopausal, defined by 1 of the following criteria:
• No spontaneous menses for ≥ 12 months
• Prior bilateral oophorectomy
• Prior hysterectomy with follicle-stimulating hormone within menopausal range

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,500/mm^3
• Absolute granulocyte count ≥ 1,500/mm^3
• No coagulation disorders

Hepatic

• SGOT and SGPT ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No major illness of the cardiovascular system

Pulmonary

• No major illness of the respiratory system

Other

• No history of cancer except squamous cell or basal cell skin cancer
• No major systemic infection
• No Cushing's syndrome or adrenal insufficiency
• No osteoporosis, defined as a bone mineral density T-score ≥ -2.5 on dual-energy x-ray absorptiometry scan (calcium and/or cholecalciferol [vitamin D] supplementation AND/OR bisphosphonate therapy allowed provided participant is on a stable dose during study participation)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• More than 3 months since prior hormone-modifying medications, including any of the following:
• Oral contraceptives
• Hormone replacement therapy
• Selective estrogen receptor modifiers
• Aromatase inhibitors
• Gonadotropin-releasing hormone modifiers
• Concurrent dehydroepiandrosterone (DHEA) allowed, provided dose remains constant during study participation

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No red wine, red grapes, or white button mushrooms directly before or during study treatment
• White and seedless grapes allowed
• No other concurrent therapy