Peoples. Our target study population is NP (or NN if negative for both ER and PR) breast cancer patients with HER2 1+ and 2+ expressing tumors who are disease-free after standard of care therapy. Disease-free subjects after or during standard of care multi-modality therapy will be screened and HLA-typed (consent #1). E75 is a CD8-eliciting peptide vaccine that is restricted to HLA-A2+ or HLA-A3+ patients (approximately two-thirds of the US population). HLA-A2+/A3+/A24+/or A26+ patients who meet all other eligibility criteria will be randomized to receive Herceptin + E75/GM-CSF or Herceptin + GM-CSF alone (consent #2). For both groups, Herceptin will be given every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy (Appendix A). The first Herceptin infusion must be given no sooner than three weeks and no later than 12 weeks after completion of standard of care therapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Herceptin will be administered as described in Section 4.3. Patients randomized to the E75/GM-CSF arm will receive vaccinations of E75 (1000 mcg) and GM-CSF (250 mcg) administered intradermally every three weeks for six total vaccinations, 30 -120 minutes after completion of Herceptin infusion. With prior approval from the Principal Investigator, the vaccine may be administered 15 minutes after completion of Herceptin infusion. The E75/GM-CSF vaccine series will begin in conjunction with the third Herceptin infusion. Starting the vaccine series after two rounds of Herceptin alone will allow for evaluation and observation for toxicities related specifically to Herceptin. In extenuating circumstances, the first vaccination may be delayed to the fourth or fifth Herceptin infusion with prior approval from the Principal Investigator. Those patients randomized to the GM-CSF alone arm will receive vaccinations of GM-CSF (250 mcg) administered in an identical manner to those receiving E75/GM-CSF. Patients will be blinded as to whether they are receiving E75/GM-CSF or GM-CSF alone. Upon completion of the vaccination series, booster inoculations (same dose and route) will be administered every six months x4 for total combination (Herceptin and vaccine) treatment duration of 30 months (Appendix A). The first booster inoculation will occur with the final Herceptin infusion, with subsequent boosters timed every six months from the first booster. Booster inoculations will occur for patients randomized to receive E75/GM-CSF as well as patients randomized to receive GM-CSF alone, and will consist of the same treatment drugs and dosing (i.e., E75/GM-CSF patients will be boosted with E75/GM-CSF while GM-CSF alone patients will be boosted with GM-CSF alone). Patient blinding will be maintained throughout the study. CONFIDENTIAL Page 16 of 102 Protocol: HERCEPTIN® + E75/GM-CSF Version 3.1 ML25749 05 March 2017 Patients will be followed for safety issues, immunologic response and clinical recurrence. Patients will be assessed 48-72 hours after each inoculation for reaction to the inoculation as well as documentation of any adverse effects experienced (Appendix A). Immunologic response will be monitored primarily by in vivo delayed type hypersensitivity (DTH) reactions but also may be documented by other immunologic assays. All patients will be followed for a total of 36 months to document disease-free status. We plan to enroll 300 patients (150 in each treatment arm) at a planned accrual rate of 10-12 patients per month (approximately 0.5-1 enrollment per study site per month). With accrual beginning in approximately April 2013, enrollment of the last patient would be expected in approximately August 2017 followed by a three-year follow-up period. The duration of the trial is expected to be seven years. 3.2 RATIONALE FOR STUDY DESIGN The recurrence rate among NP breast cancer patients with HER2 1+ and 2+ expressing tumors after standard of care therapy is reported to be 20% at 24 months. Herceptin alone (with GM-CSF) may have some benefit and decrease the rate to 15% (Baselga et al. 1998, Burstein et al.