HER2 status results in an unstable switch from primary to recurrent breast cancer

Neoplasma. 2024 Aug;71(4):392-401. doi: 10.4149/neo_2024_240229N89.

Abstract

Accurately distinguishing HER2-2+ tumors from HER2-0/1+ tumors via immunohistochemistry (IHC) is still very challenging. HER2 IHC 2+ is considered to indicate moderate expression and is easier to distinguish, with more reliable results in previous and current clinical practice. We focused on HER2-2+ patients and evaluated the switch in HER2 status between primary and paired recurrent disease patients to evaluate the discordance of HER2-2+ expression. We included patients who were HER2-2+ of primary or rebiopsy tumor samples, to evaluate the evolution of HER2-2+ expression. In the cohort with a total of 159 patients with HER2-2+ expression in either primary tumor or locoregional/distant metastasis samples, 44.0% had HER2-2+ in primary tumor and 88.8% in recurrent disease. Among patients with primary and recurrent HER2-2+ breast cancers, 18.5% and 15.2% of the patients, respectively, had HER2 gene amplification via ISH. The overall rate of discordance in HER2 IHC results was 67.1%. Among primary HER2-2+ patients, 74.6% were maintained in the HER2-2+ cohort at the recurrence. The discordance was mostly driven by patients switching from HER2-2+ to HER2-1+ (64.7%). Among HER2-2+ recurrent patients, discordance in the IHC results was mostly driven by switching from HER2-0 to HER2-2+ (47.1%). When HER2-low was added to the analysis, the overall rate of HER2 discordance was 40.4%. The proportion of patients with discordant HER2 expression was significantly greater among HR-positive patients than negative patients (44.1% vs. 21.7%, p=0.062). HER2 expression in primary and recurrent breast cancer samples was highly unstable. Discordance was more frequently observed in the HR-positive population.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Female
  • Gene Amplification
  • Humans
  • Immunohistochemistry*
  • Middle Aged
  • Neoplasm Recurrence, Local* / metabolism
  • Neoplasm Recurrence, Local* / pathology
  • Receptor, ErbB-2* / metabolism

Substances

  • Receptor, ErbB-2
  • ERBB2 protein, human
  • Biomarkers, Tumor