Effects of HLA status and HER2 status on outcomes in breast cancer patients at risk for recurrence – Implications for vaccine trial design

Immunotherapy, using peptide-based cancer vaccines is being studied to assess its potential in breast cancer. Trials of HLA-restricted peptide vaccines have been difficult to enroll given HLA subtype restrictions. It is necessary to determine the prognostic significance of HLA-status in breast cancer if patients who are ineligible to receive a vaccine due to their HLA-status are used as controls. The impact of targeted tumor associated antigen expression, when it effects eligibility is also important. We examined control patients from two randomized phase II trials that tested HER2-peptide vaccines to determine the effect of HLA-A2 status and HER2 expression on disease-free survival. The analysis showed that HLA-A2-status does not affect disease-free survival, regardless of HER2 expression suggesting that HLA-A2 negative patients can be used as control patients. Additionally, HER2 over-expression was associated with a better disease-free survival in this population, underscoring the need for additional therapies in HER2 low-expressing breast cancer. ClinicalTrials.gov Identifier: NCT00524277 •The ability of peptide-based vaccines are being investigated to decrease morbidity/mortality/recurrences of breast cancer•HLA-A2 negative patients can be used as controls in HLA-restricted therapies for breast cancer•HLA-A2 status did not affect the disease-free survival regardless of the patient’s HER2 expression•HER2 positivity was associated with better disease-free survival•There is a need for additional therapies for HER2 low-expressing breast cancer