Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin

Inclusion Criteria:

• Female Sex (Note: Patients may be pre-menopausal or post-menopausal)

• Age 18 years or older

• Histologically confirmed invasive breast carcinoma, stage I-III (Note: EstrogenReceptor (ER), Progesterone Receptor (PR) and HER2 status must be known. In newlydiagnosed patients planning neoadjuvant treatment, a formal assessment of axillarylymph nodes is not required.)

• Planning to initiate adjuvant or neoadjuvant AC (adriamycin and cytoxan)chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2-3 weeks x 4 cycles). (Note: Participants may be planning to receive adjuvant taxane therapyafter the completion of AC chemotherapy. HER2 positive patients must be planning toinitiate trastuzumab therapy after AC chemotherapy.)

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Normal organ function and marrow function as defined by:

• Absolute neutrophil count (ANC) ≥ 1,000

• Platelet count ≥ 100,000

• Total bilirubin less than or equal to the upper limit of normal

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 timesthe upper limit of normal

• Creatinine ≤1.5 times the upper limit of normal

• Creatine kinase (CK) ≤2.5 times the upper limit of normal

• Left ventricular ejection fraction (LVEF) as assessed by baseline echocardiogram ator above the lower limit of normal

• Women of childbearing potential must agree to use adequate contraception (non-hormonal or barrier method of birth control or abstinence) prior to study entryand for the duration of participation. Should a woman become pregnant or suspect sheis pregnant while participating in the study, she should inform her treatingphysician immediately

• Ability to understand the study regimen and the willingness to sign a writteninformed consent document

• Negative pregnancy test (women of childbearing potential only)

Exclusion Criteria:

• Prior anthracycline therapy

• Currently pregnant or lactating

• Currently receiving investigational agents

• Known active liver disease (cirrhosis, chronic viral hepatitis, autoimmune liverdisease or other known clinically significant active liver disease)

• Known myopathy or history of rhabdomyolysis

• Uncontrolled hypothyroidism

• History of allergic reaction or intolerance to statin treatment

• Currently receiving statin therapy or have received any statin therapy within thelast 3 months

• Known history of ischemic cardiac disease (including angina requiring anti-anginalmedications, myocardial infarction, coronary artery disease documented on cardiaccatheterization or ischemia documented on stress test), congestive heart failure,clinically significant arrhythmia or conduction system abnormalities, clinicallysignificant valvular disease, clinically significant pericardial effusion or EFbelow the lower limit of normal

• Uncontrolled inter-current illness including, but not limited to, ongoing or activeserious infection, other active cardiac disease or psychiatric illness/socialsituations which would limit compliance with study requirements

• Inability to swallow tablets or use of a feeding tube

• Gastrointestinal disease, surgery or malabsorption that could potentially impact theabsorption of the study drug

• Daily consumption of alcohol exceeding 3 standard drinks a day (defined as 10 gramsof alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL ofwine or 30 mL of liquor)

• Women currently taking drugs which are strong inhibitors or inducers of CYP3A4 arenot eligible. These may be found at the Indiana University Clinical Pharmacologywebsite at http://medicine.iupui.edu/clinpharm/ddis/main-table/.

• Women taking associated with a substantial risk of myopathy when co-administeredwith simvastatin are not eligible. These drugs are listed in the simvastatin packageinsert (available at:http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf).

• Women taking medications for which interaction with simvastatin may result inincreased levels are not eligible. Such drugs are listed in the simvastatin packageinsert (available at:http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf).

• Any medical condition which, in the opinion of the investigator, puts the patient atrisk of potentially serious complications while on study treatment