Dendritic Cell Vaccines Against Her2/Her3 and Pembrolizumab for the Treatment of Brain Metastasis From Triple Negative Breast Cancer or HER2+ Breast Cancer

female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least one of the following conditions applies:

* Not a woman of childbearing potential (WOCBP)

* A WOCBP who agrees to follow contraceptive guidance

WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood:this may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used. NOTE: If the risk of conception exists, patients must agree to use highly effective contraception throughout the study and for at least two years following the last study treatment administration

Negative serum and highly sensitive urine pregnancy test(s):

At initial screening prior to eligibility confirmation

within 72 hours prior to leukapheresis if \>72 hours have passed between screening test and the Leukapheresis visit

Pregnancy testing will be performed for WOCBP and interpreted prior to every cycle of pembrolizumab (Initial Treatment Phase);

at the End of Treatment (EOT) Assessment; and

whenever pregnancy is otherwise suspected. Note: In the event that 72 hours have elapsed between the screening pregnancy test and leukapheresis, another pregnancy test must be performed and must be negative in order for subject to undergo leukapheresis

Histologically or cytologically confirmed diagnosis of triple negative breast cancer (TNBC) (estrogen receptor \[ER\] =\< 1%, progesterone receptor \[PR\] =\< 1% HER2 negative) or HR+ breast cancer

* HER2 testing should be performed on the invasive component using a validated immunohistochemistry (IHC) or in situ hybridization (ISH) assay

* IHC staining is defined as:

* IHC 3+ if there is complete and intense circumferential membrane staining within \> 10 percent of tumor cells. All IHC 3+ tumors are considered HER2 positive

* IHC 2+ if there is incomplete and/or weak/moderate, circumferential membrane staining within \> 10 percent of tumor cells. All IHC 2+ tumors are reported as HER2 equivocal

* IHC 1+ if there is faint or barely perceptible, incomplete membrane staining within \> 10 percent of tumor cells. All IHC 1+ tumors are reported as HER2 negative

* IHC 0 if (1) no staining is observed, or (2) there is faint or barely perceptible, incomplete membrane staining within \< 10 percent of tumor cells. All IHC 0 tumors are reported as HER2 negative

* Equivocal HER2 testing should trigger reflex HER2 testing using ISH on the same specimen or a new test (using a different specimen with either IHC or ISH)

* Results from ISH are defined as the ratio of gene amplification of HER2 and the chromosome 17 enumeration probe (CEP17). Results are reported as:

* ISH positive if the HER2/CEP17 ratio is \>= 2.0, and the HER2 copy number signals/cell is \>= 4

* Definitive diagnosis will be rendered pending further workup in the following instances:

* If the HER2/CEP17 ratio is \>= 2.0 and an average HER2 copy number is \< 4.0 signals/cell - negative if confirmed on retesting

* If the HER2/CEP17 ratio is \< 2.0 and the average HER2 copy number is \>= 6.0 signals/cell positive - if confirmed on retesting

* If the HER2/CEP17 ratio is \< 2.0 and an average HER2 copy number is between \>= 4.0 and \< 6.0 signals/cell negative - if confirmed on retesting

* ISH negative if the HER2/CEP17 ratio is \< 2.0 and average HER2 copy number is \< 4.0 signals/cell

Measurable brain disease as per RANO-BM criteria modified to include the cut off point of 0.5 cm or higher. Have at least one untreated (includes irradiation) brain metastasis approved by a research team that meets the following size requirements:

* \>= 0.5 cm AND twice the magnetic resonance imaging (MRI) slice thickness; and

* \< 3.0 cm, that is asymptomatic and does not require local therapy at the time of enrollment (i.e. target lesion\[s\])

* Of note, lesions \>= 0.5 cm and \< 3 cm may be determined ineligible by the research team because of location or symptoms. An untreated brain metastasis is defined as a lesion not present at the time of whole brain radiation therapy or not included in a stereotactic radiotherapy field (or within 0.5 cm of a treated lesion), or any lesion that is new or unequivocally progressing since prior radiation therapy or prior surgery.

Any brain metastasis \>= 3.0 cm or causing symptoms must have previously been treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment. Any lesion present at the time of whole brain radiation therapy (WBRT) or included in the stereotactic radiotherapy field (or within 5 mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment

Stereotactic radiosurgery (SRS) and/or prior radiotherapy is permitted \>=2 weeks prior to initial Dendritic Cell (DC) vaccine dose (leaving one or more lesions which are not radiated and will be used as target lesions) but a follow up brain MRI should be obtained prior to dendritic cell (DC) vaccine to determine stability of the lesions. An interval of at least 4 weeks after the end of whole brain radiation or for any surgical resection of brain lesions is permitted ; an interval of at least 4 weeks or 5 half-lives (whichever is sorter) after the last cytotoxic, targeted, immunotherapeutic or investigational agent is permitted (prior to the start of DC vaccine)

* Previous whole brain radiation is allowed if patient has been diagnosed with recurrent, progressive brain metastasis. Previously irradiated lesions would be considered non-target lesions

* Previously resected lesions or those treated with SRS would be considered nontarget lesions. There is no limitation on prior local therapies to other lesions.

If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Toxicity that has not recovered to \<=Grade 1 is allowed if it meets the inclusion requirments for lab parameters (Participants with \<= Grade 2 neuropathy may be eligible)

Patients must have adequate organ and marrow function as defined below (specimens must be collected within 10 days prior to the start of study treatment):

Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L

Leukocytes: \>= 3 x 10\^9/L

Absolute neutrophil count: \>= 1.5 x 10\^9/L

Platelets: \>= 100 x 10\^9/L

Total bilirubin: =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 x ULN

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]): =\< 2.5 x institutional upper limit of normal (=\< 5 x ULN for participants with liver metastases)

Creatinine OR Measured or calculated creatinine clearance (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN

International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (APTT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

No evidence of leptomeningeal disease

If patient is on steroids, they must be on a steroid dose less than or = to an equivalent prednisone dose of 10 mg daily

Life expectancy of \> 3 months

Prior checkpoint inhibitors permitted 3 weeks prior to enrollment

If the disease has progressed on current treatment in the CNS, prior to consent, patients may continue Her 2 directed antibody treatment (trastuzumab and pertuzumab); aromatase inhibitor or tamoxifen while on the study; patients with triple negative breast cancer may continue capecitabine, eribulin or paclitaxel while on study per PI discretion

Patients with systemic disease will be managed as detailed in Section 10.1 - Patients who develop systemic disease progression on the protocol will be managed as detailed in Section 10.4.2

Rapidly progressing systemic disease which might interfere with completion of all the vaccine doses

Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed

History of allogenic tissue/solid organ transplantation

Has an active infection requiring systemic therapy which in the investigator's opinion will increase risk to the patient

Has known active hepatitis B or hepatitis C infection (Testing is not mandatory)

Has known immunosuppressive disease (e.g. human immunodeficiency virus \[HIV\], acquired immunodeficiency syndrome \[AIDS\] or other immune depressing disease). Testing is not mandatory

Has received a blood transfusion in the two weeks prior to leukapheresis

Pregnant or actively nursing (females who agree to stop nursing would be eligible) participants

Unwilling or unable to follow protocol requirements

Brain lesion size with significant midline shift or obstructive hydrocephalus

The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed unless at a low dose, not to exceed 10 mg of prednisone (or equivalent) per day

History of stroke or transient ischemic attack within 6 months prior to study enrollment

History of (non-infectious) pneumonitis /interstitial lung disease that required steroids, or has current pneumonitis/ interstitial lung disease

Presence of leptomeningeal disease

Any contraindication to MRI (i.e., patients with pacemakers or other metal implanted medical devices). An MRI safety questionnaire is required prior to MR imaging

Has received prior radiotherapy within 2 weeks of start of study treatment with dendritic cell (DC) vaccine and/or has received SRS \<2. weeks prior to the administration of the first DC vaccine dose. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-CNS disease

Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed.

Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug (DC vaccine)

Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded

A WOCBP who has a positive urine or blood pregnancy test at screening and within 72 hrs prior to leukapheresis

\*Note: in the event that 72 hrs have elapsed between the initial screening pregnancy test and leukapheresis, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to undergo leukapheresis

Known active carcinomatous meningitis

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

What this study is about