Clinical labs (baseline): a. Complete blood count which includes a differential and platelet count b. Comprehensive metabolic panel (CMP) which includes electrolytes, creatinine, blood urea nitrogen (BUN) , AST, ALT, alkaline phosphatase, and total bilirubin. 7. Research blood includes: a. 200 mls for immunologi c monitoring , including, cytokine k inetics and an assessment of single polymorphisms and T cell function that may contribute to PSK responsiveness . 8. The research staff will instruct each patient on the mixing and administration of study drug using “dummy” pouches . The study staff will ensure that they do not witness the preparation of the tea in order to preserve the study blind. 9. Immediately after the 1 st vaccine, patients will take a total dose of PSK 3000 mg/placebo while in the UW CRC. a. 30 minutes (+15 min) after the placebo/ PSK dose, 10 mls of blood will be drawn for cytokine kinetics b. 4 hours (+/-15 min), after their first dose of placebo/ PSK dose, 10 mls blood will be drawn for cytokine kinetics 7866/135 08/23/2021 Page 21 of 39 10. Day 2 a. 24 hours (+/-30 min) after finishing their first dose of placebo /PSK, patients will return to the UW CRC for an additional 10 ml s blood draw for cytokine kinetics b. After this blood draw, patients will start taking the placebo/ PSK at 1500 mg orally BID (total daily dose = 3000 mg) c. Patients will be given a sufficient amount of placebo/ PSK which will equal a 30 day supply + 7 additional days as needed, in order to provide continuous dosing until the subsequent study visit d. Patients will be given a monthly tea diary C. Monthly immuniza tions 1. The following procedures and tests will be done prior to each vaccination: a. Physical examination which includes weight, vital signs, symptom/toxicity assessment and medication/supplement changes. b. Urine pregnancy test in patients capable of child beari ng (patients found to be pregnant will not receive further study treatment ). c. Clinical labs: CBC and CMP . d. Research blood: 40 mls for immunologic monitoring 2. Monthly vaccines will be administered intradermally (i.d.) on the arm or leg for 3 months. a. Patients with axillary lymph node dissection (ALND) will have vaccine administered to the contralateral arm. Patients with bilateral ALND will have vaccine administered in the thigh. As much as possible each vaccine dose will be given within the same draining ly mph node site. b. Vaccines may be scheduled 28 + 7 days apart . 3. Post-vaccination monitoring: Patients will be observed on the UW CRC for minimum of 60 minutes and vital signs will be documented. 4. Arm 1: Patients will be given a 1- month supply + 7 additional day s of placebo agent and a monthly tea diary. 5. Arm 2: Patients will be given a 1- month supply + 7 additional days of PSK (1500 mg twice daily) and a monthly tea diary. 6. Collect any unused PSK pouches for destruction. Should patients show evidence of disease progression, they will be removed from the study if their treatment conflicts with the eligibility criteria (e.g., concurrent administration of chemotherapy, immune modulators, steroids, etc.). D. Evaluation after the final vaccine 1. One month after the final vaccination (approximately month 4) patients will undergo : a. A physical examination w hich i ncludes weight, vital signs, symptom/toxicity assessment and medication/supplement changes. b. Clinical labs : CBC and CMP c. Research blood draw of 200 mls for immunologic monitoring d. Arm 1: Patients will be given a 1 -month supply of placebo agent and a monthly tea diary. e. Arm 2: Patients will be given a 1- month supply of PSK (1500 mg twice daily) and a monthly tea diary. 2. Two months after last vaccine (approxi mately month 5) patients will undergo research blood draw of 40 mls for immunologic monitoring . 3. Three months after last vaccine (approximately month 6) toxicity information will be collected from the patient’s primary oncologist which will include recent notes and labs. Recent i maging reports may be collected if available. 4. Nine months after the last vaccine (approximately month 12) patients will undergo research blood draw of 200 mls for immunologic monitoring. 7866/135 08/23/2021 Page 22 of 39 5. Information on patient’s disease status will be obtained biannually from their primary oncologist for up to 3 years from enrollment . E. Management of Potential Study Risks Although patients have a small chance of experiencing an allergic -type reaction to the vaccine, if a reaction were to happen, it would usually occur within one hour of the vaccination. For this reason, all patients will undergo post-vaccination monitoring in the UW CRC which will include observation and monitoring of vital signs for a minimum of 60 minutes. Patients must have a baseline LVEF measured by MUGA or ECHO equal to or greater than the lower limit of normal for the facility within three months of enrollment . Subsequent LVEF monitoring while on HER2 - targeted monoclonal antibody therapy will be done per standard of care by patient’s oncologist or as clinically indicated. 9. Patient Withdrawal from Study The Principal Investigator/Study Physician may deem it appropriate to remove a patient from study participation for toxicity (as described in Section 12), recurrent disease, or other reasons. Patients who are no longer being vaccinated or provided PSK/Pl acebo may continue to be followed for disease status and/or research blood may be requested to follow immunity. Whether it was the decision of the patient or the Principal Investigator/Study Physician to withdraw participation from the study, it will be reported in the annual renewal report to all appropriate agencies. We will report the reason for the withdrawal and whether it was related to the study. Patients who have persistent grade 3 or 4 toxicity at time of withdrawal from study treatment will cont inue to be followed until toxicity resolves or returns to baseline for that patient. Patients may decide to withdraw from the study at any time and for any reason, at which time all research- related treatment procedures (vaccine and/or PSK/Placebo) will then cease. 10. Evaluation and Management of Toxicity Toxicity grading will be evaluated according to the CTEP CTCAE v. 4.0 common terminology and the DSMP (Appendix C). DLT will be defined as Grade 2 autoimmune reactions and any incidence of Grade 3 or 4 adverse events (AEs) other than those listed in Table 5. For grade 2 treatment -related reactions, patients will be treated with acetaminophen and/or diphenhydramine or as clinically indicated per standard of care; and will not receive further vaccinations or PSK. Table 5: Expected and Allowable Grade 3 Toxicities (CTCAE v4.0) that are not DLT Category Toxicity/Adverse Event Allowable Duration General disorders and administration Flu-like symptoms 1 week Musculoskeletal and connective tissue disorders Arthralgia 1 week Myalgia 1 week Investigations Lymphocyte count decreased 2 week Hemoglobin decrease 2 week White blood cells decreased 2 week Rationale for allowing the above Grade 3 toxicity is based on the following. Our proposed target population (patients with Stage 4 breast cancer who are NED or have stable bone disease) most likely have received ≥2 regimens of chemotherapy which can resul t in long -lasting grade 1 and 2 hematologic abnormalities specifically decreased WBC, lymphocyte counts and hemoglobin which are clinically insignificant (e.g., do not place patient at significant increased risk and/or require medical intervention). We ha ve extensive experience in vaccinating this patient population and it is expected that despite their Grade 1 and 2 hematologic abnormalities, these patients will have fairly normal and functional bone marrow reserve and not be at increased risk of harm due to transient perturbations in the immune system. Additionally, we have now conducted 3 HER2 vaccine studies in over 100 optimally treated patients with stage 4 NED and/or stable bone disease on trastuzumab monotherapy and have observed only transient Grade 3 hematologic toxicity that did not require medical intervention. While the incidence of transient 7866/135 08/23/2021 Page 23 of 39 Grade 3 hematologic toxicity in our previous vaccine studies is low (<2%) it can occur due to patients having low blood counts at baseline. The combinat ion of trastuzumab and pertuzumab as maintenance therapy has also been extensively studied and found to have an acceptable toxicity profile with no increased cardiotoxicity.[43] Additionally, all patients in our proposed target population will be on either trastuzumab or combination trastuzumab/pertuzumab; and the majority will be on endocrine and/or bisphosphonate therapy. All of these therapies independent of vaccination and PSK can incur flu- like symptoms, myalgias and arthralgias and enhance similar and expected symptoms related to vaccination. Lastly, PSK has not been associat ed with grade 3 flu -like symptoms, arthralgias, myalgias or hematologic toxicity (lymphopenia, anemia, or leukopenia) . We will monitor patients closely for the above Grade 3 toxicities and should they occur will only be allowed for a limited duration of 1- 2 weeks. If any of these Grade 3 toxicities exceed the 1 -2 week period, they will constitute DLT and patient would not receive further treatment. If there is a Serious Adverse Event (Appendix C; Section C), that in the opinion of the Independent Medical Monitor, may constitute increased risk to other study participants (i.e. , risk section of consent may need to be amended ), un-blinding of treatment assignment for an individual subject may be requested by the medical monitor. The study statistician would provide the code if requested directly by the medical monitor. The study team would remain blinded and would follow the recommendations of the Independent Medical Monitor to amend the necessary study documents. 11. Dose Modifications There will not be any modifications to the vaccine , PSK or placebo doses . There may be allowances for the timing of the administration of vaccine to accommodate patient schedules or special circumstances . Subsequent v accinations will be scheduled 28 + 7 days from when the previous vaccine was actually administered, not when it should have been administered. 12. Accrual and Criteria for Premature Study Termination Combination immunotherapy with HER2 -directed immunotherapy has been shown to be both safe and immunogenic. Additionally, the proposed oral dose of PSK (3000 mg/day) has been demonstrated to be safe with and without chemotherapy in large randomized breast cancer studies with the most common and expected AEs being diarrhea, nausea, vomiting, anorexia, hives and stomach discomfort (incidence of all listed AEs was <1%) . [44, 45] Although we expect minimal toxicity from HER2 vaccination administered concomi tantly with PSK, criteria for stopping the trial for excessive treatment -related toxicity will be instituted as follows: The study will be terminated for safety reasons if there is sufficient evidence to suggest that the true incidence of Grade 3 or higher toxicity exceeds 40%, the true incidence of Grade 4 toxicity exceeds 20%, or both. The toxicity rates (adverse events) will be evaluated after every 5th enrolled patient has become evaluable, and sufficient evidence will be defined as observed rates of toxicity that correspond to 1- sided 80% confidence int ervals with lower limits greater than 40% (Grade 3 or higher) or 20% (Grade 4). Operationally, these limits would be achieved if 4/5, 6/10, or 9/15 patients experienced Grade 3 or higher toxicity, or if 3/5, 4/10, or 5/15 patients experienced Grade 4 toxi city. Monitoring and reporting of AEs and toxicity rates will be done per the DSMP (Appendix C). 13. Statistical Considerations A. Study statistics 1. Determination of Sample Size: This sample size is chosen to be sufficient for gathering preliminary data on both the sa fety of PSK and its efficacy in enhancing NK cell activity when combined with HER2 vaccination and HER2 monoclonal antibody therapy in this patient population. Thirty patients will be enrolled and randomized in equal numbers to one of 2 arms (15 patients/arm) unless there is excessive toxicity as defined in Section 12. Up to 5 additional patients may be enrolled per arm to replace subjects who fail to receive study treatment to meet the target accrual of 30 subjects. 2. Randomization: Eligible subjects will be enrolled and randomly assigned in equal proportions to one of two treatment arms, Arms 1 (Placebo) and 2 (PSK) via a permuted block design. Following an algorithm developed by the study statistician, a randomization table will be generated and provided to IDS pharmacy . 7866/135 08/23/2021 Page 24 of 39 Patients , clinicians and study staff will be blinded to the treatment assignment. The dispensing UW IDS pharmacy staff will be un- blinded. a. Randomization will take place following completion of the screening evaluations and eligibility assessment. b. Patient information will be entered into the study database and patients will be assigned a unique study identification number. c. The study staff will notify the dispensing pharmacy to request the patient’s randomization. d. Patients will be randomly assigned per the randomization table described above.