Intervention: Acolbifene Hydrochloride
Trial phase: Phase 2
SMILES: CC1=C(c2ccc(O)cc2)C(c2ccc(OCCN3CCCCC3)cc2)Oc2cc(O)ccc21.Cl
Sex: Female
Age groups: Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 25
Group description: Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity.

acolbifene hydrochloride: Given orally
Eligibility criteria:
Inclusion Criteria:

Gail risk >= 1.7% and/or relative risk >= 3 times that for 5-year age group
Premenopausal
More than 6 months since initiating or discontinuing oral contraceptives
At increased risk for breast cancer, as indicated by >= 1 of the following risk factors:
BRCA1/2 mutation characterized as deleterious or of uncertain significance
Prior atypical ductal hyperplasia, ductal carcinoma in situ, or lobular carcinoma in situ
Prior random periareolar fine needle aspiration (RPFNA) showing atypical hyperplasia

Family history consistent with hereditary breast cancer, as indicated by 1 of the following criteria:

>= 4 relatives with breast cancer
>= 2 relatives diagnosed with breast cancer at ≤ 50 years of age
Breast and ovarian cancer diagnosed in same relative
No suspicion for breast cancer on baseline mammogram performed between days 1-10 of menstrual cycle within 3 months prior to screening baseline RPFNA
Exhibits hyperplasia with or without atypia (Masood score >= 14) with >= 500 cells AND Ki-67 positivity >= 2% by RPFNA performed within 6 months prior to initiation of study drug
Estimated visual mammographic breast density category >= 5% on mammogram performed within 6 months prior to initiation of study drug
Has regular menstrual cycles (between 21 and 35 days) unless using extended regimen oral contraceptives or a contraceptive device (e.g., Mirena IUD) Values for metabolic profile and blood count within normal limits
Absolute granulocyte count > 1,000/mm^3
Platelets > 100,000/mm^3
Hemoglobin > 10 g/dL
Bilirubin < 2.0 mg/dL
AST < 2 times upper limit of normal (ULN)
Albumin > 3.0 g/dL
Creatinine < 1.5 mg/dL
Alkaline phosphatase < 2 times ULN
Concurrent hormonal contraceptives allowed provided patient remains on the same hormonal regimen from 3 months prior to baseline aspiration until the completion of study treatment
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
Willing to ingest recommended dose of calcium and vitamin D for premenopausal bone health (1,200 mg calcium and 800 IU vitamin D daily)
Negative pregnancy test prior to receiving study agent

Exclusion Criteria

pregnant or nursing
nursing within the past 6 months
Known osteoporosis or severe osteopenia (T-score -2 or worse by DEXA)
History of symptomatic endometriosis with pelvic pain, poorly controlled migraines, or hot flashes
History of deep venous thrombosis
History of allergic reactions attributed to compounds of similar chemical or biological composition to the study agent
Other condition or concurrent illness that, in the opinion of the investigator, would make the patient a poor candidate for RPFNA
Less than 1 year since prior use of aromatase inhibitors (e.g., anastrozole, exemestane, or letrozole) or selective estrogen receptor modulators (e.g., tamoxifen citrate, raloxifene, or arzoxifene hydrochloride)
Other concurrent chemopreventive agents
Concurrent anticoagulants
Other concurrent investigational agents
Bilateral breast implants