Oral Tamoxifen vs. TamGel vs. Control in Women With Atypical Hyperplasia, Lobular Carcinoma In Situ, or Increased Breast Cancer Risk

Clinically suspicious mass/lesions

Breast cancer in the past 5 years.

Patients with any history of venous thromboembolic disease, regardless of timeframe (history of varicose veins and superficial phlebitis is allowed).

Current pregnancy or lactation.

History of other prior breast cancer-specific therapy within the previous 2 years (chemotherapy, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors).

Cytotoxic chemotherapy for any indication in last 2 years.

Prior use of selective estrogen receptor modulator (SERMS) or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within the past 5 years unless:

* Use was less than 6 months duration in the past 5 years and not used in the 1 year prior to enrollment, or

* Use was no greater than 2 months duration in the past 1 year and not used in the 6 months prior to enrollment.

Exogenous sex steroid, including oral contraceptive pill use within 1 month prior to pretreatment breast biopsy. Use of vaginally administered estrogens and hormone coated IUD such as Mirena is permitted.

History of any prior ipsilateral breast radiotherapy. Previous unilateral radiation of the contralateral side is allowed.

Skin lesions on the breast that disrupt the stratum corneum (e.g., eczema, ulceration).

History of endometrial neoplasia

Current smoker. Cessation for at least 6 weeks

Current users of potent inhibitors of tamoxifen metabolism. The potent inhibitors of tamoxifen metabolism are: bupropion, cinacalcet, fluoxetine, paroxetine, quinidine.

Participants may not be receiving any other investigational agents within 90 days of enrollment or during this study.

History of allergic reactions to tamoxifen.

Uncontrolled intercurrent illness that in the judgement of the treating physician would make them unsuitable for study participation

Current use of anticoagulation medications.

Patients who are breastfeeding.

Hemoglobin \< 10 g/dL (within 30 days of randomization).

Leukocytes \< 3,000/microliter (within 30 days of randomization).

Platelets \< 100,000/microliter (within 30 days of randomization).

Total bilirubin \> 1.5 x institutional upper limit of normal (ULN) (within 30 days of randomization).

Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) \> 1.5 x ULN (within 30 days of randomization).

Alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) \> 1.5 x ULN (within 30 days of randomization).

Alkaline phosphatase, S \> 1.5 x ULN (within 30 days of randomization).

Albumin, S \> 1.5 x ULN (within 30 days of randomization).

Protein, total, S \> 1.5 x ULN (within 30 days of randomization).

Creatinine \> 1.5 x ULN (within 30 days of randomization).

Antithrombin III \<80% of normal.

Fibrinogen \>1000 mg/dL.

Patients who are taking any medications, herbal products, or over the counter (OTC) products that are moderate or strong CYP2D6 inhibitors or CYP3A inducers. Patients should also refrain from starting any drug or product with these properties during the study. This is to avoid any potential interactions with tamoxifen or 4-OHT.

Clinically significant arrhythmia requiring ongoing medication for control / treatment, especially those with high risk of QT prolonging effects.

Identification of a clinically suspicious mass on examination.

What this study is about