Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast

Inclusion Criteria:

• Screen-detected, estrogen receptor (ER) positive DCIS of the breast proven on coreneedle biopsy, defined as 10% positive cells; the presence of a focus suspicious formicroinvasion will be allowed; the size of the DCIS in the core biopsy sample musttotal 5 mm (multiple cores can be summed) and must be estimated on the deepest stepsection (if step sections are taken)

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

• Participants must have acceptable organ and marrow function as defined below:

Baseline lab parameters are not standard of care for initiation of tamoxifen therapy; a minimal panel will therefore be appropriate.

• Leukocytes >= 3,000/microliter

• Absolute neutrophil count >= 1,500/microliter

• Platelets >= 100,000/microliter

• Total bilirubin within "≤1.5 x institutional upper limit of normal (ULN)institutional limits

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal (ULN)

• Creatinine within "≤1.5 x institutional upper limit of normal (ULN) institutionallimits

• Women of childbearing potential and their male partners must agree to use TWOeffective forms of birth control (abstinence is not an allowed method) prior tostudy entry and for the duration of study participation, and for two monthsfollowing the last dose of study medications; effective birth control methods are:copper IUD [intrauterine device], diaphragm/cervical cap/shield, spermicide,contraceptive sponge, condoms; women of childbearing potential must have a negativeurine pregnancy test within seven days before starting study medications; should awoman become pregnant or suspect she is pregnant while participating in this study,she should inform her study physician immediately

• Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e.tanning beds) for the duration of the study

• Ability to understand and the willingness to sign a written informed consentdocument

Exclusion Criteria:

• DCIS presentation as a palpable mass

• Exogenous sex steroid use within 4 weeks prior to core needle biopsy

• Prior ipsilateral breast cancer radiotherapy will be excluded; prior contralateralbreast cancer therapy within 2 years will also be excluded

• Skin lesions on the breast that disrupt the stratum corneum (eg eczema, ulceration)

• History of endometrial neoplasia

• History of thromboembolic disease (history of varicose veins and superficialphlebitis is allowed)

• Current smokers

• Current users of potent inhibitors of tamoxifen metabolism must be able todiscontinue their use and switch to an alternative medication for the duration ofparticipation, under the advice of their physician; if the physician feels that analternative medication is not appropriate for the subject and the current medicationis medically necessary, the subject will not be eligible; the drugs are listedbelow; many of these are not in clinical use at the moment; bupropion, celecoxib,chlorpheniramine, chlorpromazine, cimetidine, citalopram, clemastine, clomipramine,clozapine, cocaine, delavirdine, desipramine, diphenhydramine, doxepin, duloxetine,escitalopram, fluoxetine, haloperidol, halofantrine, hydroxyzine, imipramine,isoniazid, ketoconazole, methadone, methimazole, mibefradil, miconazole,nicardipine, paroxetine, pergolide, perphenazine, pioglitazone, pyrimethamine,quinidine, quinine, ranitidine, ritonavir, ropinirole, sertraline, terbinafine,thioridazine, ticlopidine, tranylcypromine, trazodone, tripelennamine

• Prior use of SERMS or AIs including tamoxifen, raloxifene, anastrozole, letrozole,or exemestane for prevention or therapy within 5 years

• Participants may not be receiving any other investigational agents within 30 days ofenrollment or during this study

• History of allergic reactions attributed to tamoxifen or compounds of similarchemical or biologic composition

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements

• Pregnant women are excluded from this study; breastfeeding should be discontinued bynursing mothers who agree to participate in the study

• Men are excluded from this study since DCIS of the breast is exceedingly rare inmen, and there are no data regarding skin penetration of 4-OHT though male chestwall skin (which is thicker and hairier than female chest wall skin)