Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer

Inclusion Criteria:

* Participants must be pre- or post-menopausal
* Participants must have a diagnosis of DCIS made by core needle biopsy
* Participants must be human leukocyte antigen (HLA)-A2 positive
* Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 (Karnofsky \>= 60%)
* Clinical chemistry less than 2 x normal upper limit of normal range
* Platelets \>= 100,000/mm\^3
* Hemoglobin \>= 10 g/dL
* Blood urea nitrogen \< 2 x upper limit of normal (ULN)
* Alkaline phosphatase \< 2 x ULN
* Lactate dehydrogenase \< 2 x ULN
* Creatinine \< 2 x ULN
* Bilirubin \< 2 x ULN
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2 x ULN
* A normal ejection fraction, as defined by the participant's institution; only limited echocardiograms (ECHOs) will be used as cardiac evaluation; no other tests are allowed; ECHO is to be done only in HLA-A2 positive participants; if ECHO has been done within 30 days prior to randomization and results showing a normal ejection fraction have been obtained prior to randomization, an additional ECHO is not needed at baseline
* Willingness to comply with all study interventions and follow-up procedures
* The ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

* Invasive breast cancer; areas of microinvasion or suspicious for microinvasion on the core biopsy is allowed
* History of prior breast cancer treated within the past two years; patients completing all breast cancer-specific treatment over two years prior to the current diagnosis are eligible
* History of prior ductal carcinoma in situ (DCIS) treated within the past two years; patients completing all treatment for a previous diagnosis of DCIS over two years prior to the current diagnosis are eligible
* Prior lobular carcinoma in situ (LCIS) is allowed
* Pregnant, unwilling to use adequate contraception during study treatment duration or breastfeeding; the effects of NeuVax on the developing human fetus are unknown; for this reason and because NeuVax may be teratogenic, pregnant women will be excluded; all heterosexually active women who may become pregnant must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation OR be post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of menstrual period for 2 years in women with a prior history of chemotherapy exposure who were pre-menopausal prior to chemotherapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Any autoimmune disease or other medical condition that, in the opinion of the investigator, would compromise the subject's safety
* Immune deficiency diseases such as immunoglobulin deficiency or immunosuppressive therapy that might interfere with appropriate immune response
* Known history of or known active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
* Patients on chronic steroid therapy or other immunosuppressive therapy except for topical or inhaled steroids known to have low systemic absorption
* Patients with a known hypersensitivity to GM-CSF, yeast-derived products, or any component of the GM-CSF product (e.g., mannitol)
* Concurrent treatment with other investigational agent
* History of non-breast malignancy within 5 years prior to randomization, except curatively treated superficial bladder cancer, carcinoma in situ of the cervix (stage 0-1), and basal cell or squamous cell carcinoma of the skin
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to NeuVax
* 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 would limit compliance with study requirements
* No recent or planned immunotherapy