low accrual

RATIONALE: Ground flaxseed may prevent breast cancer in premenopausal women at increased risk of developing primary breast cancer.

PURPOSE: This randomized clinical trial is studying how well flaxseed works in preventing breast cancer in premenopausal women at risk of breast cancer.

OBJECTIVES:

Primary aims:

• Determine if 25 grams of flaxseed supplementation daily

  • modifies proliferation (ki-67) and apoptotic rates after six months
  • modifies expression of estrogen regulated genes: Cyclin D1, survivin, and VEGF at six months
  • modifies serum IGF-1 and serum binding protein (IGFBP)-3 levels from baseline to 6 months
  • and evaluate the feasibility and tolerability of flaxseed consumption, and determine factors that lead to decreased compliance

STUDY OUTLINE:

This is a randomized study. Patients are randomized to 1 of 2 arms.

• Arm I (intervention): Patients ingest 25 grams ground flaxseed daily, with already prepared foods, for 6 months. Patients are instructed to record the time and with what foods flaxseed is consumed, and the number of bowel movements daily. Throughout the 6-month intervention period, patients also complete unannounced telephone-administered surveys recounting all foods and beverages consumed within the previous 24 hours.
• Arm II (observation): Patients do not receive ground flaxseed. All patients complete a diary about menstrual cycle duration and presence or improvement of premenstrual symptoms (e.g., cramping, bloating, headache, insomnia, or other irregular symptoms). Patients also complete questionnaires at 1, 3, and 6 months to access changes in diet, physical activity, menstrual history, demographic characteristics, and medical history and a specimen questionnaire at baseline and at 1, 3, and 6 months.

Blood and first-void urine samples are collected at baseline and at 1, 3, and 6 months to measure levels of lignan metabolites, flaxseed compliance, serum thiocyanate, malondialdehyde, and for biomarker studies by capillary gas chromatography-mass spectrometry, high-performance liquid chromatography, and ELISA.

After completion of study therapy, patients are followed monthly for up to 6 months.

• Patients enrolled in must meet ≥ 1 of the following criteria:

  • History of unilateral or bilateral atypical ductal hyperplasia with or without family history
  • History of atypical lobular hyperplasia or lobular carcinoma in situ with or without family history
  • History of ductal carcinoma in situ
  • Prior stage I breast cancer allowed provided it was adequately treated and therapy was completed ≥ 1 year ago
  • Lifetime risk for developing breast cancer > 20% (based on Gail or Claus model)
  • No abnormal mammogram requiring short-term follow-up within the past 6 months
  • No severe atypia or carcinoma cells on RPRNA

PATIENT CHARACTERISTICS:

• Premenopausal

• ECOG performance status 0-1

• Patients enrolled must meet the following criteria:

  • No peri- or postmenopausal status as determined by estradiol levels < 20 ng/dL and FSH levels > 45 ng/dL

  • No thrombocytopenia (defined as platelet count < 50,000/mm^3)

  • Creatinine ≤ 1.5 mg/dL

  • Not pregnant or nursing

  • Fertile patients must use effective contraception consistently

  • No other prior malignancy allowed except for the following:

    • Basal cell or squamous cell carcinoma
    • In situ cervical cancer

  • No history of any of the following conditions within the past 5 years:

    • Crohn disease
    • Ulcerative colitis
    • Inflammatory bowel disease
    • Irritable bowel syndrome
    • Celiac sprue
    • Malabsorption syndrome
    • Diverticulitis
    • Diverticulosis

  • No allergy to flaxseed, other seeds or nuts, or wheat

PRIOR CONCURRENT THERAPY:

• Patients enrolled in part 1 must meet the following criteria:

  • No prior breast implants or tram-flap reconstruction

    • Breast reduction allowed

  • No prior neoadjuvant chemotherapy or other chemotherapy within the past year

  • No prior neoadjuvant hormonal therapy

  • No prior whole radiation to the contralateral breast undergoing random periareolar fine needle aspiration (RPFNA)

  • No concurrent coumadin or other chronic anticoagulants (even if they are held for surgery)

• Patients enrolled in part 2 must meet the following criteria:

  • More than 1 year since prior chemotherapy and adjuvant hormonal therapy for breast cancer

    • No concurrent chemotherapy for breast cancer

  • At least 1 month since prior and no concurrent treatment with corticosteroid

  • At least 2 weeks since prior and no concurrent use of antibiotics

  • At least 2 weeks

  • No history of chest wall irradiation

  • No presence of breast implants

  • No prior or concurrent tamoxifen within the past 90 days

  • No chronic/concurrent medications that inhibit platelet function, including any of the following:

    • Aspirin

    • Non-steroidal anti-inflammatory drugs (i.e., Aleve®, Motrin®, ibuprofen)

    • Coumadin

    • Heparin

    • Low molecular weight heparin

    • Anti-platelet agents

      • No prior short-term use of platelet inhibitors ≥ 7 days prior to RPFNA

  • No concurrent ingestion of the following:

    • Pumpkin seeds
    • Sesame seeds
    • Fish oil supplements

  • At least 30 days since prior and no concurrent flaxseed supplements, fish oil, or flaxseed oil

  • No concurrent treatment for another malignancy