Immune Response and Potential Booster for Patients Who Have Received HER2-pulsed DC1

• HER2 DC1 Vaccine (Biological), also known as Vaccine: Ultrasound (US) guided intranodal delivered vaccines will be administered at each participating site by a radiologist experienced in ultrasound guided procedures along with the principal investigator or his/her designee. Each dose will consist of between 1.0-2.0 x 10\^7 cells and will be injected into 1 right and 1 left normal groin lymph nodes.

Primary outcomes

• HER2 DC1 Vaccine Regimen [Up to 16 months]: Investigators will assess the feasibility of participants receiving the six-booster regimen if 11/15 randomized to Arm D complete all 6 booster injections.

Secondary outcomes

• HER2 Immunity with 3 Booster Regimen at 18 months [At 18 months after first dose]: To compare the overall average effects of two different vaccine regimens on anti-HER2 CD4 immunity (ELISPOT) at 18 months from month 1 injection. treatment among women with breast cancer previously treated with HER2 vaccines. Two regimens consist of 3 versus 6 booster HER2 vaccine injections administered every 3 months
• HER2 Immunity with 6 Booster Regimen at 18 months [At 18 months after first dose]: To compare the overall average effects of two different vaccine regimens on anti-HER2 CD4 immunity (ELISPOT) at 18 months from month 1 injection. treatment among women with breast cancer previously treated with HER2 vaccines. Two regimens consist of 3 versus 6 booster HER2 vaccine injections administered every 3 months
• HER2 Immunity with 3 Booster Regimen at 10 months [At 10 months after first dose]: To compare the overall average effects of two different vaccine regimens on anti-HER2 CD4 immunity (ELISPOT) at month 10 from first vaccine treatment
• HER2 Immunity with 6 Booster Regimen at 10 months [At 10 months after first dose]: To compare the overall average effects of two different vaccine regimens on anti-HER2 CD4 immunity (ELISPOT) at month 10 from first vaccine treatment
• Rate of Treatment Emergent Adverse Events of 3 Dose Regimen [Up to 5 years]: Serious adverse events will be recorded for 100 days after study treatment. Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• Rate of Treatment Emergent Adverse Events of 6 Dose Regimen [Up to 5 years]: Serious adverse events will be recorded for 100 days after study treatment. Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• Overall Survival [Up to 5 Years]: OS will be measured using the Kaplan-Meier method
• Disease Free Survival [Up to 5 Years]: DFS will be measured using the Kaplan-Meier method
• Progression Free Survival [Up to 5 Years]: PFS will be measured using the Kaplan-Meier method

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Patients with a diagnosis of nonmetastatic or metastatic breast cancer in complete clinicla response classic HER2pos (ie, IHC 3+ or FISHpos) breast cancer (BC) who have previously been vaccinated with DC1 HER2-pulsed vaccines on any of several prior clinical trials for ductal carcinoma in situ (DCIS) or inflammatory breast cancer (IBC) are eligible; however, we also allowed HER2 2+ patients in many of these prior trials and they will also be allowed to participate in this trial. Note: HER2pos BC is defined by tumor tissue HER2 overexpression and or tumor HER2 amplification. The lack of HER2 overexpression by IHC is defined as 0 or 1+ whereas overexpression is defined as 3+. In the event of equivocal IHC, 2+, the tumor must be gene-amplified by fluorescent in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio > 2 and HER2 copy number > 4 define HER2negdisease).
* Patients with nonmetastatic HER posBC must have completed all standard-of-care treatment for nonmetastatic BC (e.g., surgery, chemotherapy, radiation therapy, and HER2-targeted therapy). Note: antiestrogen therapy is permitted while on trial. Note: antiestrogen therapy is permitted while on trial.
* Patients with diagnosis of metastatic HER2 pos breast cancer must have complete tumor response to current treatment per RECIST 1.1 and completed all standard-of-care chemotherapy. Note: maintenance treatment with approved HER2-targeted agents and/or antiestrogen therapy is permitted while on trial.
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Participants must have normal organ and marrow function within 2 weeks of registration.
* For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose.
* Must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

Exclusion Criteria:

* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congenital prolonged QT syndrome, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Uncontrolled congenital or acquired immune deficiency that is requiring treatment that would interfere with study treatment will not be allowed on study. Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed. Patients who have received systemic corticosteroids ≤ 30 days prior to starting study drug will be excluded.
* No other prior malignancy is allowed except for the following:

  * Adequately treated basal cell or squamous cell skin cancer
  * In situ cervical cancer
  * Any other cancer from which the patient has been disease free for at least 3 years.
* Pregnant or breast feeding.
* Known to be HIV positive.
* Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared.
* Major surgery within 4 weeks of initiation of study drug.
* Have not recovered to ≤ Grade 1 or tolerable Grade 2 adverse events (AEs) due to agents administered ≥ 28 days earlier, as documented by the treating investigator.
* Currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug. Note: patients enrolled on another HER2 vaccine trial but not receiving active therapy can enroll in this study.
* Not able to comply with the treatment schedule and study procedures for any reason.

• Ricardo Costa, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute