Digoxin in Treating Patients with Stage I-III Breast Cancer Planning to Undergo Surgery

Inclusion Criteria

• Histologically confirmed infiltrating carcinoma of the breast (stage I-III)
• Unresected disease that meets the following criteria: * Scheduled to undergo definitive surgery (lumpectomy or mastectomy) * Tumor size >= 1 cm (radiographically or clinically) * Grade 2 or 3 tumor or Ki-67 proliferation index of >= 10% (or both) * Any estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status; however, receptors must have been tested on a diagnostic specimen * NOTE: bilateral cancers are eligible as long as at least 1 tumor meets the eligibility criteria above; if possible, tissue should be collected from both cancers at the time of tissue collection * A patient planning to initiate preoperative therapy who would like to take part in the study may do so if she agrees to undergo a study biopsy at the completion of digoxin dosing and prior to start of treatment, or at any time prior to start of treatment in those patients randomized to receive no drug; in these patients, tissue from the definitive surgery may still be collected for study correlates at the discretion of the protocol chair and pathologist
• Patients must not have received any prior treatment of any kind to treat the current breast cancer – including chemotherapy or endocrine therapy; in addition, any history of prior irradiation to the ipsilateral breast is excluded
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky 80%-100%)
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Bilirubin (total) less than or equal to the upper limit of normal; an exception to this may be allowed for participants with Gilbert’s syndrome with prior approval by the protocol chair
• Creatinine =< 1.5 times the upper limit of normal with creatinine clearance >= 50 mL/min using the modified Cockcroft-Gault method
• Thyroid stimulating hormone (TSH) within normal limits
• Serum magnesium within normal limits
• Serum potassium within normal limits
• Serum sodium within normal limits
• Serum calcium within normal limits
• Women of child-bearing potential must agree to use adequate contraception (non-hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Women who are pregnant or nursing
• Current use of any investigational agents
• Radiological evidence of metastatic disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to digoxin
• Concomitant use of these drugs at baseline and for the duration of digoxin administration (if randomized to receive it): * The calcium channel blockers diltiazem or verapamil * Cardiac arrhythmic agents (such as quinidine, amiodarone) * Other cytochrome P450 (P450) inducer/inhibitors * NOTE: patients already receiving digoxin are also excluded; patients who take calcium carbonate antacids (e.g., Maalox, Tums, Rolaids) or antidiarrheal adsorbents (kaolin and pectin) should avoid taking these at the same time as the digoxin dose
• Presence of any of the following on electrocardiogram (ECG): * Atrial arrhythmias, including atrial fibrillation and flutter * Atrioventricular (AV) block * Heart rate < 60 beats/minute unless the participant is otherwise eligible, without significant cardiac concerns and approval is obtained by the protocol chair/study cardiologist prior to enrollment * Heart rate > 100 beats/minute * Ventricular fibrillation * Ventricular tachycardia * Premature ventricular contractions * Wolff-Parkinson-White syndrome * NOTE: any questions on cardiac eligibility should be reviewed by the Study Cardiologist for approval in advance of enrollment
• History of any of the following, unless approval is given by the Protocol Chair: * Heart disease, including acute myocardial infarction * Cardiac arrhythmias, including sick sinus syndrome * Pulmonary disease with a known forced expiratory volume (FEV) of < 1.5 or on oxygen * Gastrointestinal disease, surgery or malabsorption that could potentially impact the absorption of the study drug * Patients requiring the use of a feeding tube * Inability to swallow tablets
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that will limit compliance with study requirements
• Any medical condition which in the opinion of the investigator puts the patient at risk of potentially serious complications while on this therapy