Inclusion Criteria:
* Patients must be at least ≥ 18 years of age
* Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in patients \< 18 years of age, children and adolescents are excluded from this study, but will be eligible for future pediatric trials, if applicable
* Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 2
* Histologically confirmed triple-negative breast cancer
* Tumors with estrogen receptor (ER)-low (≤ 5%) or negative and progesterone receptor (PR)-low (≤ 5%) or negative will be included
* HER2-negative or HER2-low will be defined by the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2023 "Human Epidermal Growth Factor Receptor 2 (HER2) Breast Testing Guideline Update" which reaffirms the 2018 "HER2 Breast Testing Guideline Focused Update"
* Tumor is negative for PD-L1 marker testing per standard of care immunohistochemistry 22C3 pharmDx assay
* Metastatic disease that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
* Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment. This site should not be a site that is used to determine measurable disease for efficacy purposes. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions
* Patients should not have received any prior cancer immunotherapy in the metastatic setting
* Prior Food and Drug Administration (FDA)-approved antibody drug conjugates are allowed
* Patients are appropriate candidates to receive standard of care chemotherapy as per treating oncologist's clinical judgement
* Patients who have received prior neoadjuvant or adjuvant chemotherapy are allowed
* A minimum of 14 days washout since last systemic therapy or any palliative radiotherapy is required
* Treatment with a bisphosphate or denosumab concurrently with protocol-specific therapy is allowed while on study (it is not exclusionary)
* Patients must be at least 28 days post systemic steroids prior to enrollment, unless this is a steroid administered concurrently with chemotherapy or used as part of prophylaxis to prevent intravenous (IV) contrast reactions
* 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 or condition precluding protocol treatment
* Willing to undergo up to two serial biopsies while on study
* White blood cell (WBC) ≥ 2500/mm\^3 (Within 28 days of receiving first study vaccine)
* Lymphocyte count ≥ 500/mm\^3 (Within 28 days of receiving first study vaccine)
* Absolute neutrophil count (ANC) ≥ 1000/μL (Within 28 days of receiving first study vaccine)
* Hemoglobin (Hgb) ≥ 9 g/dL (Within 28 days of receiving first study vaccine)
* Platelets ≥ 75,000/μL (Within 28 days of receiving first study vaccine)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be \< 3.0 mg/dL (Within 28 days of receiving first study vaccine)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (Within 28 days of receiving first study vaccine)
* Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance \> 60 mL/min (Within 28 days of receiving first study vaccine)
* Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. Effective methods of contraception must be used throughout the study until the end of treatment on study
Exclusion Criteria:
* Patient has received more than one line of prior therapy in metastatic setting
* Patients with tumors that are PD-L1-positive per standard of care immunohistochemistry 22C3 pharmDx assay
* Enrollment in a concurrent interventional clinical trial. Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed
* 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 with any autoimmune disease or comorbidities that require chronic systemic steroids or immunosuppressants. Patients with conditions requiring inhaled, intranasal or topical steroids are permitted
* Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF
* A non-breast malignancy requiring radiation or systemic therapy within last 5 years or any B-cell malignancy (e.g., chronic lymphocytic leukemia or follicular lymphoma) under active surveillance
* Pregnant and breastfeeding individuals
* Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive), or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
* Major surgery within the 4 weeks prior to initiation of study vaccine
* Must be 14 days between a non-study vaccine, including live attenuated and non-live vaccines and any STEMVAC vaccination
* Note: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine
* Any condition that may interfere with the patient's participation in the study per treating physician