Breast cancer is a tumor entity that is one of the leading causes of mortality among women worldwide. Although numerous treatment options are available, current explorations of personalized vaccines have shown potential as promising new treatment options to prevent the recurrence of cancer. Here we present a small proof of concept study using a prophylactic peptide vaccination approach in four female breast cancer patients who achieved remission after standard treatment. The patients were initially analyzed for somatic tumor mutations and then treated with personalized neoantigen-derived peptide vaccines. These vaccines consisted of HLA class I and class II peptides and were administered intracutaneously followed by subcutaneous application of sargramostim and/or topical imiquimod as an immunological adjuvant. After an initial priming phase of four vaccinations within two weeks, patients received monthly boosting/maintenance vaccinations. Chemotherapy or checkpoint inhibition was not performed during vaccination. One patient received hormone therapy. The vaccines were well tolerated with no serious adverse events. All patients displayed vaccine-induced CD4+ and/or CD8+ T-cell responses against various neoantigens. Furthermore, all patients remained tumor-free and had persistent T-cell responses, even several months after the last vaccination, suggesting the potential of peptide vaccines as an immunosurveillance and long term prophylaxis option.