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

PRIMARY OBJECTIVES: I. To demonstrate that 2 mg once daily per breast of 4-hydroxytamoxifen (4-OHT) topical gel results in a reduction in the Ki-67 labeling index of ductal breast carcinoma in situ (DCIS) lesions that is not inferior to that seen with 20 mg daily oral tamoxifen citrate (TAM) for 4-10 weeks, when comparing the base-line diagnostic core biopsy to the therapeutic surgical excision sample. SECONDARY OBJECTIVES: I. To compare post-therapy changes in the oncotype DCIS-score between arms (this is a validated reverse transcriptase-polymerase chain reaction \[RT-PCR\] assay for Ki67, STK15, survivin, cyclin B1, MYBL2, PR, GSTM1). II. To compare between-group post-therapy changes in immunohistochemistry (IHC) markers: CD-68 macrophage marker as a surrogate for response to therapy, p16 and COX-2. III. To compare post-therapy changes in breast density, quantitative estimate, between arms. IV. To compare post-therapy breast tissue and plasma levels of TAM and its metabolites (N-desmethyl tamoxifen \[NDT\], \[E\] and \[Z\] isomers of 4-hydroxytamoxifen \[4-OHT\], N-desmethyl-4-hydroxytamoxifen \[endoxifen\]). V. To compare post-therapy breast tissue and plasma levels of estradiol and progesterone between arms (optional). VI. To compare the post-therapy fraction of participants demonstrating "no residual DCIS". VII. To compare post-therapy changes in plasma proteins involved in coagulation: factors VIII and IX, von Willebrand factor, total protein S between arms. VIII. To compare post-therapy changes in plasma markers of systemic estrogenic effect (IGF-1, SHBG). IX. To compare post-therapy changes in symptoms as captured in the breast cancer prevention trial (BCPT) Eight Symptom Scale (BESS) questionnaire and skin reactions to 4-OHT gel. OUTLINE: Patients are randomized into 1 of 2 arms. ARM I: Patients apply afimoxifene gel to both breasts and receive placebo orally (PO) daily for 4-10 weeks in the absence of disease progression or unexpected toxicity. ARM II: Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are followed up at 1-2 weeks and 1 month after surgery.