Secondary Endpoints : a. Evaluation of the effect of PSK on NK cell functional activit y. PBMC will be obtained and cryopreserved at baseline (prior to start of PSK) and then at 4, 8, and 16 weeks . PBMC will subsequently be thawed and used to determine the effect of PSK on NK cell functional activity specifically, induction of IFN -γ production and CD107a expression in NK cells, via flow cytometr y. Augmentation of NK cell activity is defined by a 2- fold increase in NK cell IFN -γ production and CD107a expression from baseline and after 4 weeks of oral adm inistration of PSK. 3. Tertiary Endpoints : a. Assessment of the effect of PSK on pro-inflammatory serum cytokine and/or chemokines when given with HER2 -directed immunotherapy . Serial blood draws will be done at baseline before the initial dose of PSK (time 0) and 30 min, 4 hours, and 24 hours after the initial dose of PSK to assess serum cytokines/chemokines (i.e., IL- 6, IFN -γ, TNF -α) via Luminex analysis. Serum cytokine/chemokine levels at different timepoints post -PSK will be compared to base -line. Serum will be cryopreserved and subsequently be thawed at time of analysis. b. Assessment of the effect of PSK on intermolecular epitope spreading when given with HER2 - directed immunotherapy . PBMC will be obtained and cryopreserved prior to the 1st vaccine and at 1 and 9 months after the 3rd vaccine (months 4 and 12) by IFN -γ ELISPOT . PBMC will subsequently be thawed and used to determine T cell precursor frequency specific for tumor antigens, HER2, IGFBP -2, TOPO -IIα, p53, and PRAME. A positive immune response wil l be defined as a T cell precursor frequency > 1:20,000 antigen- specific PBMCs. Development of a positive immune response after treatment begins will constitute augmentation in patients without pre-existent immune responses. In patients with pre -existent immune response to the tumor antigens, augmentation is defined as a final response to tumor antigen >2 times the baseline level. Epitope spreading will be defined as the generation of significant immunity to the HER2 ECD as the patients will receiv e an IC D vaccine. c. Assessment of the effect of PSK on serum TGF -β levels when given with HER2 -directed immunotherapy . Serum TGF- β levels will be assessed via ELISA prior to the 1st vaccine (baseline), and 1, and 9 months after the 3rd vaccine (months 4 and 12) to determine the incidence and magnitude of reduction of serum TGF -β levels pre - and post -combination immunotherapy. A decrease in serum TGF -β levels will be defined as a reduction of ≥ 25% from baseline value to post-vaccination values. Serum will be cr yopreserved and subsequently be thawed at time of analysis. d. Evaluation of PFS and OS . PFS and OS will be followed and compared between study arms. This study will not enroll sufficient numbers of subjects to give statistical power to this endpoint however, large differences if observed between the treatment groups ( PSK + HER2 -directed immunotherapy versus Placebo + HER2 -directed immunotherapy ) will be noted and described. PFS and OS will 7866/135 08/23/2021 Page 20 of 39 be defined as time from first vaccine t o time of first event. While on study, patients will be followed for disease progression by their primary oncologist per conventional practice standards. Information on patient disease status will be obtained biannually from their primary oncologist for up to 3 years after enrollment . 8. Plan of Treatment - Arms 1 and 2 The following section outlines the patient evaluation and treatment schedule prior to and during study. A. Pre Screen Potential subjects will be screened for eligibility by a study team member. Standard- of-care procedures, done prior to signing consent , can be used for eligibility assessment as long as they are conducted within required windows (Section 6). During this evaluation a pathology report will be obtained to ensure a patient’s tumor is HER2 positive as described in Section 6. B. Initial evaluation (may be performed up to 2 weeks prior to initial vaccine visit) 1. Sign consent form before initiating any study procedures and eligibility is confirmed. 2. The clinical trial procedures wi ll occur at the UW CRC. Patients , who meet the inclusion/exclusion criteria after consent, will be assigned a unique study numbers and randomized to either PSK or placebo at time of study visit #1 – Day 1. Following an algorithm developed by the study statistician, a randomization table will be generated and provided to an un -blinded IDS pharmacist . Patients, clinicians, and study staff will be blinded to treatment assignment. a. Arm 1 : Patients will be a ssign ed to the placebo agent b. Arm 2 : Patients will be assigned to PSK 3. Medical history and complete physical examination which includes weight, vital signs, symptom assessment , Zubrod scoring, medication/supplement changes (Appendix A). 4. Urine pregnancy testing will be performed on female patients of childbearing potential . If a patient is found to be pregnant, she will not be able to participate in the study. 5. A tetanus -diphtheria vaccine (Td) will be administered as a positive control if patient has not received Td immunization within the last six months. Patients who have experienced any of the following described under a. and b. below will not receive the Td vaccine but will continue all other study related treatment and procedures. • Patients that have ever had a life- threatening allergic reaction after a dose of any tetanus or diphtheria containing vaccine, OR have had a severe allergy to any part of a tetanus or diphtheria vaccine. • Patients with epilepsy or another nervous system problem, severe pain or swelling after any vaccine containing diphtheria or tetanus, or ever had Guillain Barré Syndrome (GBS). 6.