A population-based study on trajectories of HER2 status during neoadjuvant chemotherapy for early breast cancer and metastatic progression

Br J Cancer. 2024 Sep;131(4):718-728. doi: 10.1038/s41416-024-02777-6. Epub 2024 Jun 28.

Abstract

Background: This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications.

Methods: This is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007-2020 in the Stockholm-Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification.

Results: In total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status.

Conclusion: HER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.

Keywords: HER2 change; HER2-low; breast cancer; neoadjuvant chemotherapy; prognosis.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Disease Progression*
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Metastasis
  • Neoplasm, Residual
  • Prognosis
  • Receptor, ErbB-2* / metabolism
  • Sweden / epidemiology

Substances

  • Receptor, ErbB-2
  • ERBB2 protein, human