Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission

This phase I trial studies the side effects and best dose of a vaccine therapy in preventing cancer from coming back in patients with non-metastatic, node positive, human epidermal growth factor receptor (HER)2 negative breast cancer in which all signs and symptoms have disappeared. Vaccines made from deoxyribonucleic acid (DNA) may help the body build an effective immune response to kill tumor cells. Giving multiple vaccinations may make a stronger immune response and prevent or delay the return of cancer.

OUTLINE: This is a dose escalation study of WOKVAC.

Patients receive WOKVAC with sargramostim intradermally (ID) on day 1. Courses repeat every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients with axillary lymph node dissection (ALND) will have vaccine administered to the contralateral arm. Patients with bilateral ALND will have vaccine administered in the thigh. As much as possible each vaccine dose will be given within the same draining lymph node site. Patients will be monitored for a minimum of 60 minutes post vaccine administration.

After completion of study treatment, patients are followed up at 1 month, 6 months and annually for up to 5 years thereafter.

Eligibility Criteria:
Inclusion Criteria:

* Patients with non-metastatic, node positive, HER2 negative breast cancer, confirmed by pathology report, who are in remission and defined as having no evidence of disease (NED); HER2 negative is defined as

  * 0-1+ HER2 expression by immunohistochemistry (IHC) OR
  * Fluorescence in situ hybridization (FISH) negative OR
  * HER2 2+ and FISH negative
* Patients must be at least 28 days post cytotoxic chemotherapy, radiotherapy, monoclonal antibody and/or other biologic therapy, prior to enrollment; patients on bisphosphonates, denosumab, and/or endocrine therapy administered during the study are eligible and may continue throughout duration of study
* Patients must be at least 28 days post systemic steroids prior to enrollment
* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 2
* White blood cell (WBC) \>= 3000/mm\^3
* Hemoglobin (Hgb) \>= 10 g/dl
* Lymphocyte count \>= 800/mm\^3
* Platelet count \>= 75,000/mm\^3
* Serum creatinine =\< 2.0 mg/dl or creatinine clearance \> 60 ml/min
* Total bilirubin =\< 1.5 mg/dl
* Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) =\< 2 times upper limit of normal (ULN)
* Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment
* The effects of WOKVAC on the developing human fetus are unknown. For this reason, patients who are having sex that can lead to pregnancy must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) for the duration of study participation; should a woman become pregnant while participating in the study, she should inform her study doctor immediately and will not receive any more study treatment
* Left ventricular ejection fraction (LVEF) results must be \>= lower limit of normal (LLN) for institution performing based on results from the multi-gated acquisition (MUGA) or echocardiogram (ECHO) done at baseline
* Willing to not undergo any elective surgical procedure with general anesthesia or conscious sedation through the 1 month post-vaccination visit
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients with any of the following cardiac conditions:

  * Symptomatic restrictive cardiomyopathy
  * Dilated cardiomyopathy
  * Unstable angina within 4 months prior to enrollment
  * New York Heart Association functional class III-IV heart failure on active treatment
  * Symptomatic pericardial effusion
* Patients may not be receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to WOKVAC
* Patients with any contraindication or known hypersensitivity to receiving sargramostim (recombinant human granulocyte macrophage colony stimulating factor \[rhuGM-CSF\]) or other yeast based products
* Pregnant women are excluded from this study because WOKVAC is a vaccine agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with WOKVAC breastfeeding should be discontinued if the mother is treated with this vaccine
* History of diabetes
* Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
* History of autoimmunity that has not been controlled with treatment in the last 12 months