TPIV100 and Sargramostim for the Treatment of HER2 Positive, Stage II-III Breast Cancer in Patients With Residual Disease After Chemotherapy and Surgery

Inclusion Criteria:

* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Histologically confirmed adenocarcinoma of the breast stage \>= T2 OR \>= N1 based on the 7th edition of tumor, node, metastases (TNM) staging system from the American Joint Committee on Cancer
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any estrogen receptor (ER) or progesterone receptor (PR) but HER2 positive defined as 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR gene amplification on fluorescence in situ hybridization (FISH) ratio \>= 2.0
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willingness to provide adequate pretreatment biopsy sample

  * NOTE: Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide \>= 3 core needle biopsies with at least 14 gauge (G) needle with 12 unstained sections of 5 micron thickness. Fine needle aspiration (FNA) sample alone is not sufficient
  * NOTE: Patients without adequate pretreatment biopsy samples must be agreeable to have an additional research biopsy prior to neoadjuvant therapy
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to employ adequate contraception from the time of pre-registration through 6 months after the final vaccine cycle
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to receive a tetanus vaccination if subject has not had one =\< 1 year prior to pre-registration
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Provide written informed consent
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to provide mandatory tissue and blood samples for correlative research purposes
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Negative pregnancy test done =\< 7 days prior to pre-registration, for persons of childbearing potential only

  * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* REGISTRATION (SAFETY LEAD-IN): Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 28 days prior to registration)
* REGISTRATION (SAFETY LEAD-IN): Platelet count \>= 75,000/mm\^3 (obtained =\< 28 days prior to registration)
* REGISTRATION (SAFETY LEAD-IN): Hemoglobin \>= 9.0 g/dL (obtained =\< 28 days prior to registration)
* REGISTRATION (SAFETY LEAD-IN): Direct bilirubin \< 1.5 x upper limit of normal (ULN) (obtained =\< 28 days prior to registration)
* REGISTRATION (SAFETY LEAD-IN): Aspartate transaminase (AST) =\< 3 x ULN (obtained =\< 28 days prior to registration)
* REGISTRATION (SAFETY LEAD-IN): Creatinine =\< 2 x ULN (obtained =\< 28 days prior to registration)
* REGISTRATION (SAFETY LEAD-IN): Prothrombin time (PT)/international normalized ratio (INR)/ partial thromboplastin time (PTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant (obtained =\< 28 days prior to registration)
* REGISTRATION (SAFETY LEAD-IN): Completed planned curative breast surgeries (not including any future breast reconstructive surgery) and any radiation therapy \>= 30 days prior to registration
* REGISTRATION (SAFETY LEAD-IN): Completed last cycle of chemotherapy \>= 90 days prior to registration

  * NOTE: Prior to registration, patients must not receive \> 8 cycles of TDM-1 maintenance therapy after surgery
* REGISTRATION (SAFETY LEAD-IN): Any residual disease after trastuzumab +/- pertuzumab based neoadjuvant chemotherapy warranted T-DM1 as per treating physician
* REGISTRATION (SAFETY LEAD-IN): Adequate tissue specimens from both pre-treatment biopsy and surgery must be submitted. Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide \>= 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness

  * NOTE: Fine needle aspiration (FNA) sample alone is not sufficient
* REGISTRATION (SAFETY LEAD-IN): Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only

  * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* REGISTRATION (SAFETY LEAD-IN): ECOG performance status (PS) 0, 1, 2
* REGISTRATION (SAFETY LEAD-IN): Willing to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): ECOG performance status (PS) 0, 1, 2
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 28 days prior to registration)
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Platelet count \>= 75,000/mm\^3 (obtained =\< 28 days prior to registration)
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Hemoglobin \>= 9.0 g/dL (obtained =\< 28 days prior to registration)
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Direct bilirubin \< 1.5 x upper limit of normal (ULN) (obtained =\< 28 days prior to registration)
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Aspartate transaminase (AST) =\< 3 x ULN (obtained =\< 28 days prior to registration)
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Calculated serum creatinine clearance of \>= 50 mL/minute (min.) (obtained =\< 28 days prior to registration)
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): PT/INR/PTT =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =\< 28 days prior to registration)
* REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Negative pregnancy test done =\< 7 days prior to registration, for person of childbearing potential

  * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 28 days prior to randomization)
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Platelet count \>= 75,000/mm\^3 (obtained =\< 28 days prior to randomization)
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Hemoglobin \>= 9.0 g/dL (obtained =\< 28 days prior to randomization)
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Direct bilirubin \< 1.5 x upper limit of normal (ULN) (obtained =\< 28 days prior to randomization)
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Aspartate transaminase (AST) =\< 3 x ULN (obtained =\< 28 days prior to randomization)
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Creatinine =\< 2 x ULN (obtained =\< 28 days prior to randomization)
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): PT/INR/PTT =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant (obtained =\< 28 days prior to randomization)
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Completed last cycle of chemotherapy \>= 90 days prior to randomization

  * NOTE: Prior to randomization, patients must not receive \>= 6 cycles of T-DM1 maintenance therapy after surgery
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Have residual disease with \>= 1 cm residual tumor in the breast (\>= ypT1c) and/or persistent lymph node positivity after trastuzumab +/- pertuzumab based neoadjuvant chemotherapy
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Adequate tissue specimens from both pre-treatment biopsy and surgery must be submitted. Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide \>= 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness

  * NOTE: Fine needle aspiration (FNA) sample alone is not sufficient
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Negative pregnancy test done =\< 7 days prior to randomization, for persons of childbearing potential only

  * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): ECOG performance status (PS) 0, 1, 2
* RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Willing to employ adequate contraception from the time of randomization through 6 months after the final vaccine cycle

Exclusion Criteria:

* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): 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 person
  * Nursing person unwilling to stop breast feeding
  * Person of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Clinical evidence of active local recurrence or distant metastases

  * NOTE: All patients must have either a positron emission tomography (PET)/computed tomography (CT) or CT chest, abdomen, and pelvis with bone scan to rule out distant metastases =\< 365 days prior to preregistration. If any of these is concerning, follow-up imaging or biopsy should be performed if indicated rule out distant metastases
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): 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
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids

  * NOTE: Must be off systemic steroids at least 14 days prior to pre-registration. However, topical steroids, inhalants or steroid eye drops are permitted
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): 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
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): 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 =\< 6 months prior to pre-registration
  * Significant cardiac arrhythmia or unstable angina
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Receiving any other investigational agent
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Other active malignancy at time of pre-registration or =\< 3 years prior to preregistration

  * 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
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): 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
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any prior hypersensitivity or adverse reaction to granulocyte-macrophage colony stimulating factor (GM-CSF)
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): History of trastuzumab-related cardiac toxicity requiring interruption or discontinuation of therapy, even if left ventricular ejection fraction (LVEF) fully recovered
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Baseline LVEF \< 50%
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): History of myocardial infarction =\< 168 days (6 months) prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias
* PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer =\< 2 months prior to pre-registration