Experimental Design A. Study design This will be a phase I/II double- blind randomized two-arm clinical trial designed to examine the safety and immune effects of PSK when given as combination immunotherapy with a HER2 ICD peptide vaccine in patients with Stage IV HER2+ breast cancer receiving HER2 -targeted monoclonal antibody therapy . Eligible patients will be enrolled and randomly assigned in equal numbers to one of two treatment arms (15 patients per arm) shown below. However, s tagger enrollment of 2 weeks will occur for the first 2 patients in each arm . Arm 1 : HER2 ICD vaccine + HER2 -targeted monoclonal antibody therapy * + Placebo: Patients will receive HER2 ICD peptide vaccine administered concomitantly with HER2 -targeted monoclonal antibody therapy and placebo product. Arm 2 : HER2 ICD vaccine + HER2 -targeted monoclonal antibody therapy * + PSK : Patients will receive HER2 ICD pept ide vaccine administered concomitantly with HER2 -targeted monoclonal antibody therapy and PSK. *Trastuzumab (or trastuzumab and pertuzumab) administered per standard of care by patient’s primary oncologist . All study patients will receive the HER2 ICD vaccine administered monthly for a total of 3 vaccines in addition to HER2 -targeted monoclonal antibody therapy (administered per standard dosing guidelines). Additionally, patients randomized to Arm 1 will receive continuous placebo product given orally and patients randomized to Arm 2 will receive continuous PSK given orally at 3000 mg/day (1500 mg twice daily before meals). Both the placebo product in Arm 1 and PSK in Arm 2 will be started on the day of the first HER2 vaccine and continued for a total of 4 months. All patients will be followed for immune response at designated timepoints as shown in the patient treatment schema below. Patient Treatment Schema 7866/135 08/23/2021 Page 19 of 39 B. Sample size The study will accrue a maximum of 30 subjects : 15 subjects per arm as described in Section 13 (Statistical Considerations ). C. Outcome measures 1. Primary Endpoints : a. Evaluation of safety of PSK when administered with HER2 -directed immunotherapy . Evaluation of safety and systemic toxicity includes physical examination and clinical labs performed at baseline, before each vaccination, and 1 month after the 3rd vaccine. Toxicity grading will be evaluated per CTEP CTCAE 4.0. Type and grade of toxicit ies noted during treatment will be summarized. Additionally, stopping rules for accrual to the study will become operational if there is sufficient evidence of excessive toxicity as described in Section 12. 2.