STEMVAC vaccine with hormone therapy plus CDK4/6 inhibitor or capecitabine for metastatic HR-positive, HER2-negative breast cancer

Inclusion Criteria:

* Patients must be at least ≥ 18 years of age
* Histologically confirmed hormone receptor positive metastatic breast cancer: Tumors that are positive for estrogen receptor (ER) and/or progesterone receptor (PR)
* HER2-negative or HER2-low will be included and defined as:

  * 0-1+ HER2 expression by immunohistochemistry (IHC) OR
  * Fluorescence in situ hybridization (FISH) negative OR
  * HER2 2+ and FISH negative
  * HER2 low per standard of care in breast cancer
* Patients should be receiving the following therapies to be eligible for the study:

  * Cohort 1: First or second line of endocrine therapy in the metastatic setting, in combination with a CDK4/6 inhibitor. Patients must have completed at least 2 cycles of CDK4/6 inhibitor. Patients who have stopped endocrine therapy for intolerance but remain on abemaciclib monotherapy will be considered for enrollment at the PI's discretion
  * Cohort 2: Progressed on endocrine-based therapies and after completion of at least 1 cycle of capecitabine
* Subjects with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or 1
* Willing to undergo up to two serial biopsies while on study
* Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment
* White blood cell (WBC) ≥ 2000/mm\^3 (within 28 days of receiving the study vaccine)
* Lymphocyte count ≥ 500/mm\^3 (within 28 days of receiving the study vaccine)
* Absolute neutrophil count (ANC) ≥ 800/µL (within 28 days of receiving the study vaccine)
* Platelets ≥ 75,000/µL (within 28 days of receiving the 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 the study vaccine)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN) (within 28 days of receiving the study vaccine)
* Creatinine ≤ 2.0 mg/dL or creatinine clearance \> 30 mL/min (within 28 days of receiving the 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 female of child-bearing potential. Acceptable methods of contraception are 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 postmenopausal. Effective methods of contraception must be used throughout the study and until the end of treatment on study
* 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

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
  * Uncontrolled hypertension
  * Uncontrolled cardiac arrhythmias
* Patients with any autoimmune disease/comorbidity that require chronic steroids or immunosuppressants
* A non-breast malignancy requiring radiation or systemic therapy within last 5 years
* Known hypersensitivity reaction to the granulocyte-macrophage colony-stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF
* Pregnant or breast feeding
* 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
* Current use of immunosuppressive agents or systemic corticosteroids. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are allowed. Patients who have received systemic corticosteroids ≤ 30 days prior to starting study drug will be excluded
* Patient is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug

  * NOTE: Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed
* Must be 14 days between a non-study vaccine 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 oncologist