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: Estrogen
Receptor (ER), Progesterone Receptor (PR) and HER2 status must be known. In newly
diagnosed patients planning neoadjuvant treatment, a formal assessment of axillary
lymph 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 therapy after the
completion of AC chemotherapy. HER2 positive patients must be planning to initiate
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 times
the 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 at or
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 entry and for the
duration of participation. Should a woman become pregnant or suspect she is pregnant
while participating in the study, she should inform her treating physician immediately

- Ability to understand the study regimen and the willingness to sign a written informed
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 liver
disease 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 the last
3 months

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

- Uncontrolled inter-current illness including, but not limited to, ongoing or active
serious infection, other active cardiac disease or psychiatric illness/social
situations 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 the
absorption of the study drug

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

- Women currently taking drugs which are strong inhibitors or inducers of CYP3A4 are not
eligible. These may be found at the Indiana University Clinical Pharmacology website
at http://medicine.iupui.edu/clinpharm/ddis/main-table/.

- Women taking associated with a substantial risk of myopathy when co-administered with
simvastatin are not eligible. These drugs are listed in the simvastatin package insert
(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 in
increased levels are not eligible. Such drugs are listed in the simvastatin package
insert (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 at
risk of potentially serious complications while on study treatment