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

Clin Immunol. 2018 Oct:195:28-35. doi: 10.1016/j.clim.2018.06.008. Epub 2018 Jul 17.

Abstract

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.

Keywords: Breast Cancer; HER2 expression; HLA-status; Immunotherapy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / mortality
  • Cancer Vaccines / immunology*
  • Female
  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • HLA-A2 Antigen / genetics*
  • Humans
  • Immunotherapy / methods*
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Recurrence, Local
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / immunology
  • Research Design
  • Risk
  • Survival Analysis
  • Treatment Outcome
  • Vaccination
  • Vaccines, Subunit

Substances

  • Cancer Vaccines
  • HLA-A2 Antigen
  • Vaccines, Subunit
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT00524277