S0812 High Dose Cholecalciferol in Premenopausal Women at High-Risk for Breast Cancer

DISEASE CHARACTERISTICS:

• At an elevated risk of breast cancer by at least one of the following criteria:

• Diagnosis of ADH, ALH, lobular carcinoma in situ (LCIS) or resected ductal carcinoma in situ (DCIS) or small invasive breast cancers (pTmi or pT1a N0) if no pior RT, tamoxifen, or systemic breast cancer treatment within 28 days prior to registration OR diagnosis of resected Stage I (T1b-c N0-N1mi) through Stage II breast cancer for which the participant has been disease-free for at least 5 years and has completed all adjuvant treatment OR

• A known* deleterious mutation in BRCA1, BRCA2, PTEN, or TP53 NOTE: *The participant must be a documented carrier to meet this criterion. If there is a known mutation in a hereditary breast cancer susceptibility gene in a participant's family member, the participant herself must have undergone genetic testing as per NCCN clinical guidelines to be eligible per this criterion.

• Modified Gail Model/CARE model** risk at 5 years ≥ 1.67% or lifetime risk ≥ 20% by Claus, BRCAPro, Tyrer-Cuzick or IBIS models OR

• Mammographic density ≥ 50% (heterogenously dense) NOTE: **Risk models are to be used only if there is no known previous diagnosis of resected DCIS or LCIS and there is no known deleterious mutation in BRCA1, BRCA2, PTEN, or TP53.

• At least one breast available for imaging and biopsy (a previously irradiated breast [i.e., for resected DCIS] is not evaluable for breast imaging or biopsy)

• Baseline mammogram (performed within 10 days after starting their last menstrual period on a digital mammography machine) that shows either normal or benign findings

• Baseline mammographic density > 10% based upon the classification system (2 = 11-50%, "scattered fibroglandular densities"; 3 = 51-75%, "heterogeneously dense"; 4 = >75, "extremely dense". Women with a baseline mammographic density of ≤ 10% (1 = ≤ 10% breasts are almost entirely fat)will not be eligible.

PATIENT CHARACTERISTICS:

• Premenopausal, defined as ≥ 1 of the following criteria:

• Less than 6 months since the last menstrual period, no prior bilateral oophorectomy, and no use of hormone-replacement therapy

• Has undergone a prior hysterectomy but no prior bilateral oophorectomy AND follicle-stimulating hormone values measured within the past 28 days are consistent with the normal values for the premenopausal state

• Zubrod performance status 0-1

• Serum creatinine ≤ upper limit of normal (ULN)

• Serum calcium or corrected calcium ≤ ULN

• Spot urine calcium:creatinine ratio < 0.37 mg/dL

• INR ≤ 1.5 times ULN+

• PT and PTT ≤ ULN*

• Baseline serum 25(OH)D level ≤ 32 ng/mL (or 80 nmol/L)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other prior malignancy except for the following:

• Adequately treated basal cell or squamous cell skin cancer

• In situ cervical cancer

• Adequately treated stage I or II (including resected Stage I, T1b-c N0-N1mi through Stage II breast cancer) from which the participant is currently in complete remission

• Any other cancer (including contralateral breast) for which the participant has been disease-free for ≥ 5 years

• No history of kidney stones

• No medical conditions requiring calcium or vitamin D supplementation (i.e., osteoporosis)

• No known hypersensitivity to vitamin D

• No known allergy to soy NOTE: +For patients undergoing breast biopsy.

PRIOR CONCURRENT THERAPY:

• Prior breast reduction surgery allowed

• No bilateral breast implants

• More than 1 month since prior surgery or radiotherapy to the breast for resected DCIS

• At least 28 days since prior tamoxifen

• Prior anticoagulant therapy allowed provided it is discontinued ≥ 7 days before breast biopsy

• No concurrent calcium or additional vitamin D supplements

• Concurrent multivitamins allowed provided that the dose of vitamin D in the multivitamin does not exceed 400 IU daily

• No concurrent participation in any other clinical trial for the treatment or prevention of cancer unless the participant is no longer receiving the intervention and is in the follow-up phase only (participants must not join such a trial while participating in this study)