A Vaccine (H2NVAC) Before Surgery for the Treatment of HER2-Expressing Ductal Carcinoma In Situ

Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Patients must not have received any prior therapy for current DCIS

  * Note: Patients who received tamoxifen, raloxifene, aromatase inhibitor or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least 2 months prior to baseline study biopsy if they chose to have this collected
  * Note: Concurrent use of endocrine therapy during the vaccination/preoperative period is not allowed. However, standard adjuvant endocrine therapy with tamoxifen or aromatase inhibitor after completion of vaccination and surgery is allowed
* Any degree of HER2 expression as performed on the diagnostic clinical biopsy defined by immunohistochemistry +1, +2, or +3
* Histologically confirmed un-resected operable ductal carcinoma in situ with no evidence of lymph node involvement or distant metastasis

  * Note: suspected microinvasion or definite microinvasion (\< 0.1 mm invasion) on core biopsy is allowed
* Patients will be asked to have an additional research biopsy prior to the first vaccination. This is not mandatory for participation
* Patients must have evidence of at least 0.5 cm of disease extent based on mammogram, ultrasound, or magnetic resonance (MRI) imaging
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (less than or equal to 28 days prior to registration)
* Platelet count \>= 75,000/mm\^3 (less than or equal to 28 days prior to registration)
* Hemoglobin \>= 9.0 g/dL (less than or equal to 28 days prior to registration)
* Creatinine =\< 2 x upper limit of normal (ULN) (less than or equal to 28 days prior to registration)
* Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2 x ULN (less than or equal to 28 days prior to registration)
* Albumin \>= 3 g/dL (less than or equal to 28 days prior to registration)
* Negative serum pregnancy test done =\< 7 days prior to Registration, for women of childbearing potential only
* Willing to employ adequate contraception from the time of Registration through 6 months after the final vaccine cycle

  * Note: Adequate contraception methods include birth control pills, barrier device, intrauterine device, or abstinence
* Capable of understanding the investigative nature, potential risks, and benefits of the study
* Capable of providing valid informed consent
* Willing to return to enrolling institution for all study visits (immunizations, blood draws, etc)
* Willing to provide blood samples for correlative research purposes
* Willing to receive a tetanus vaccination if subject has not had one within the past year

Exclusion Criteria:

* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

  * Pregnant women
  * Nursing women unwilling to stop breast feeding
  * Women of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids, unless physiologic replacement for adrenal or pituitary insufficiency

  * Note: Must be off systemic steroids greater than or equal to 90 days prior to Registration. However, topical steroids, inhalants or steroid eye drops are permitted
* 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
* Uncontrolled acute or chronic medical conditions including, but not limited to the following:

  * Active infection requiring antibiotics
  * Congestive heart failure with New York Heart Association class III or IV moderate to severe objective evidence of cardiovascular disease
  * Myocardial infarction or stroke less than or equal to 6 months prior to registration
* Receiving any other investigational agent
* Other active malignancy at time of registration or less than or equal to the last three years prior to registration. EXCEPTIONS: Non-melanoma skin cancer or carcinoma-in-situ (e.g. of cervix, prostate)

  * NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for their cancer
* Known history of active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-registration

  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded
* Any prior hypersensitivity or adverse reaction to GM-CSF
* History of trastuzumab-related cardiac toxicity requiring interruption or discontinuation of therapy, even if left ventricular ejection fraction (LVEF) fully recovered
* Baseline LVEF with a value below 55%
* Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
* History of myocardial infarction =\< 168 days (6 months) prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias
* History of ipsilateral radiation to the current affected breast with DCIS