Genistein in Preventing Breast Cancer in Women at High Risk for Breast Cancer

PRIMARY OBJECTIVE:

I. Determine the effect of genistein on the proliferation of breast epithelial cells obtained by fine needle aspiration (FNA), as measured by Ki-67 labeling index, in women who are at high risk for breast cancer.

SECONDARY OBJECTIVE:

I. Determine the effect of this drug on cellular and molecular parameters using epithelial cells obtained by FNA, nipple aspirate fluid, and blood from these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal) and history of breast cancer (no history of breast cancer vs history of estrogen receptor [ER] positive breast cancer vs history of ER negative breast cancer). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral genistein once daily.

ARM II: Patients receive oral placebo once daily.

In both arms, treatment continues for up to 6 months in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed at 30-37 days.

Inclusion criteria

• No known soy intolerance
• At increased risk of developing breast cancer in >= 1 previously unaffected breast, as defined by any of the following:

• Estimated 5-year risk of developing breast cancer using the Gail model, as defined by 1 of the following:

• Gail score >= 1.66%
• Gail score >= 0.1% for women age 20-29 years
• Gail score >= 1.0% for women age 30-39 years
• Estimated 5-year risk of developing breast cancer using the Claus model:

• Claus score >= 1.66%
• Claus score >= 0.1% for women age 20-29 years
• Claus score >= 1.0% for women age 30-39 years
• Prior diagnosis of unilateral in situ or invasive breast cancer OR history of atypical hyperplasia, BRCA 1 and/or BRCA 2 positivity
• History of lobular carcinoma in situ
• No evidence of breast cancer, as determined by a negative mammogram within the past 6 months and a history and physical
• No previously diagnosed breast cancer unless all systemic therapy (including endocrine therapy) was completed at least 1 year ago
• Pre- or postmenopausal
• ECOG performance status 0-1
• Hemoglobin > 10.0 g/dL
• Platelet count > 100,000/mm^3
• Absolute neutrophil count > 1,000/mm^3
• Creatinine < 2.0 mg/dL
• SGPT < 82 U/L
• SGOT < 68 U/L
• Bilirubin < 3 mg/dL* [Note: * Patients with a higher level of bilirubin due to a familial metabolism may be eligible at the discretion of the investigator]
• Life expectancy > 2 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• Must be willing to keep a dietary diary
• No venous thrombosis within the past year
• No unrecognized or poorly controlled thyroid disease
• No other cancer within the past 5 years except nonmelanomatous skin cancer or noninvasive cervical cancer
• No other medical condition that, in the opinion of the investigator, would jeopardize either the patient or the integrity of the data obtained
• None of the following for >= 2 weeks before the first random fine needle aspiration and during study participation:

• Oral contraceptives
• Soy supplements
• High soy-containing foods
• Fish oil supplements
• Multivitamins
• Vitamins C and E
• Daily aspirin or nonsteroidal
• Anti-inflammatory drugs
• No other concurrent investigational agents
• No concurrent warfarin or other blood thinners
• Female patient

Exclusion criteria

Women previously diagnosed with breast cancer will not be eligible unless all systemic therapy (including endocrine therapy) was completed at least one year previously

• Currently pregnant, or planning to become pregnant during the study period
• History of venous thrombosis within past year
• Medical conditions, which, in the opinion of the investigators would jeopardize either the patient or the integrity of the data obtained
• History of other cancer within the past five years, excluding non-melanomatous skin cancer, and non-invasive cervical cancer
• Known soy intolerance
• Unrecognized or uncontrolled thyroid disease, subjects may be on synthroid, but thyroid function must be in normal range or the patient's physician must document that the patient's thyroid is controlled.
• Currently receiving any other investigational agents
• Currently on coumadin, or other blood thinners
• History of breast augmentation implants.
• Rusults from patients who have <4000 epithelial cells in either the first or the second random Fine-needle aspiration (rFNA) will not be included in the study.