Letrozole With and Without Simvastatin for the Treatment of Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer

Eligibility Criteria

• * Age \>= 18 years
• * Biopsy proven hormone receptor positive, HER2 negative stage I-III invasive breast cancer
• * Estrogen receptor (ER) and/or progesterone receptor (PR) positivity are defined as \>= 10% of cells expressing hormonal receptors via IHC analysis
• * HER2 negativity is defined as either of the following by local laboratory assessment
• * IHC 0, 1+, or 2+ and in situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 \< 2.0 or single probe average HER2 gene copy number \< 4 signals/cell)
• * Minimum primary tumor size 5 mm on any breast imaging (mammogram, ultrasound, magnetic resonance imaging \[MRI\])
• * Baseline Ki-67 IHC expression on tumor tissue \>= 10%
• * Post-menopausal women
• * Prior bilateral oophorectomy
• * Age \>= 55 years
• * Age \< 55 and amenorrheic for 12 months or more in the absence of chemotherapy, endocrine therapy, or ovarian suppression and follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol in the postmenopausal range
• * Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• * Prior treatment:
• * No systemic therapy (chemotherapy, immunotherapy, endocrine therapy, and/or investigational therapy) within 3 months of trial enrollment
• * No statins, fibrates, or ezetimibe within 3 months of trial enrollment
• * No active liver disease
• * Hemoglobin \>= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 9.0 g/dl is acceptable) (within 14 days prior to initiation of study treatment)
• * Absolute neutrophil count (ANC) \>= 1,500/mcL (after at least 7 days without growth factor support or transfusion) (within 14 days prior to initiation of study treatment)
• * Platelets \>= 100,000/mcL (within 14 days prior to initiation of study treatment)
• * Total bilirubin =\< 2 institutional upper limit of normal (ULN) (within 14 days prior to initiation of study treatment)
• * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 institutional ULN (within 14 days prior to initiation of study treatment)
• * Serum creatinine =\< 2 mg/dL (or glomerular filtration rate \>= 40 mL/min) (within 14 days prior to initiation of study treatment)
• * Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
• * Be willing and able to provide written informed consent for the trial
• * Patients who are receiving any other investigational agents or an investigational device within 3 months before administration of first dose of study drugs
• * History of allergic reactions attributed to compounds of similar chemical or biologic composition to simvastatin and/or letrozole
• * Concomitant use of strong CYP3A4 inhibitors (i.e. clarithromycin, erythromycin, itraconazole, ketroconazole, nefazodone, Posaconazole, voriconazole, protease inhibitors \[including boceprevir and telaprevir\], telithromycin, cobicistat-containing products), cyclosporine, danazol, and gemfibrozil
• * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, substance abuse disorders, or psychiatric illness/social situations that would limit compliance with study requirements
• * Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association class 3 or 4 congestive heart failure; or uncontrolled grade \>= 3 hypertension (diastolic blood pressure \>= 100 mmHg or systolic blood pressure \>= 160 mmHg) despite antihypertensive therapy
• * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy