Vaccine aims to block return of aggressive breast cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age \>= 18 years * Female * Resected unilateral or bilateral primary carcinoma of the breast without clinical evidence of metastatic disease (after neoadjuvant chemotherapy and/or adjuvant chemotherapy), negative for estrogen receptor (ER) and progesterone receptor (PR) (cut-off for positivity is \> 10% positive tumor cells with nuclear staining), and negative for HER2 as defined by one of the four situations delineated below: * HER2 immunohistochemistry (IHC) expression of 0 or 1+ and in-situ hybridization non-amplified * HER2 IHC expression of 0 or 1+ and in-situ hybridization not done * HER2 IHC expression of 2+ and in-situ hybridization non-amplified * IHC not done and in-situ hybridization non-amplified * Note: central review is not required * Note: If biopsy and surgical specimens are discordant from each other with regard to ER, PR, and/or HER2 status, a patient will be allowed to enroll assuming at least one of the specimens meets the above criteria and no endocrine therapy use is planned going forward * Completed planned breast CANCER surgeries, any radiation therapy, and any chemotherapy, whichever is last, \>= 90 days but not \>= 546 days prior to randomization * Note: Reconstructive and prophylactic surgeries are allowed after randomization (during study treatment) * Patient had at least one of the following: * Biopsy or surgery-proven regional node involvement by cancer * T1c, T2, T3, or T4 disease (with inflammatory disease allowed) identified at the time of surgery or clinically identified prior to neoadjuvant chemotherapy * No complete response to neoadjuvant chemotherapy (those who did achieve complete response are still eligible if a pre-chemotherapy regional nodal biopsy identified cancer or if the pre-chemotherapy tumor measured \> 1 cm) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 * Absolute neutrophil count (ANC) \>= 1500/mm\^3 obtained =\< 14 days prior to randomization * Platelet count \>= 75,000/uL obtained =\< 14 days prior to randomization * Aspartate transaminase (AST) =\< 3 x upper limit of normal (ULN) obtained =\< 14 days prior to randomization * Creatinine =\< 1.5 x ULN obtained =\< 14 days prior to randomization * Negative serum pregnancy test done =\< 14 days prior to randomization, for women of childbearing potential only * Provide informed written consent * Willing to return to enrolling institution for follow-up * Willing to provide tissue and blood samples for correlative research studies 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 * Women of childbearing potential who are unwilling to employ adequate contraception * Clinical evidence of local recurrence or distant metastases; Note: New primary tumors are allowed, both contralaterally and ipsilaterally, but a prior breast cancer must have been more than 5 years beforehand * Known hypersensitivity reaction to GM-CSF * Active autoimmune disease that has required systemic treatment =\< 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization; 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 * 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 * NOTE: Localized fungal or viral infections including of the skin, nails, mouth, and genital area are allowed * History of other cancer \< 5 years prior to consent (except non-melanoma skin cancer or carcinoma in situ of the uterine cervix) or current receipt of treatment another cancer (e.g., monoclonal antibody, small molecule pathway inhibitor) * Treatment with systemic corticosteroid or immune-modulators =\< 7 days prior to randomization * Concurrent treatment with other experimental drugs or any other systemic anticancer therapy (due to unknown drug-vaccine potential interactions). Use of experimental or other targeted therapy \> 3 months prior is allowed as long as it is not Her2-directed * NOTE: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), statins, and other medications commonly used to treat nononcologic, non-autoimmune conditions are allowed * Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy * Prior or concurrent use of trastuzumab or other Her2-directed therapy * Prior or concurrent use of a PD-1 or PD-L1 checkpoint inhibitor (including pembrolizumab) unless the use was \>= 3 months prior to randomization