The duration of the trial is expected to be five years. 3.2 Rationale for study design In HER2-positive breast cancer patients who receive neoadjuvant chemotherapy plus trastuzumab, the 3-year Kaplan-Meier estimates of RFS are 95.7% for patients that achieve a pCR versus 80.1% for patients that do not achieve a pCR 16 Protocol: 2014-0443 Version 2.1 Version Date: 11 April 2016 (p=.02). 24 For HER2-positive breast cancer patients that undergo surgery as a first intervention and are found to be node-positive, 5-year DFS rates are 72% for those with 4 or more positive lymph nodes and 78% for those with 1-3 positive lymph nodes. 15 Based on preliminary data, the combination of trastuzumab plus a CTL-eliciting HER2-derived peptide vaccine virtually eliminated recurrences. This current study will add to these data by investigating the combination of trastuzumab and nelipepimut-S+GM-CSF in an adequately powered randomized clinical trial. 3.3 Outcome measures 3.3.1 Primary outcome measure Disease state will be determined by the patients’ own physicians at the individual study sites during their routine follow-up screening. This will occur for all enrolled patients, regardless of randomization, approximately every three months for the first 24 months after completion of primary therapies and every six months thereafter with clinical exam, laboratory (CBC and CMP) and radiographic surveillance as indicated. Evaluation of the patients’ labs will be performed approximately every 3 months during the primary series and approximately every 6 months during the booster phase to monitor for potential toxicity from the study drug combination. This follow-up strategy is standard of care for these patients.