Breast biomarkers evolution between primary and distant metastasis: incidence and significance

Histopathology. 2025 Apr;86(5):793-804. doi: 10.1111/his.15387. Epub 2024 Dec 17.

Abstract

Aims: To evaluate the evolution when breast cancer (BC) is classified as three clinical profiles and five clinical profiles by incorporating human epidermal growth factor 2 (HER2)-low to the biomarkers' profile.

Methods and results: BC with distant metastasis that has document hormonal receptors (HR) (positive, negative) and HER2 (positive, low, zero) results were included (n = 161). Cases were categorised into three clinical profiles (HR-positive/HER2-negative, HER2-positive and TNBC) and five (HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, HR-negative/HER2-low, HR-positive or negative/HER2-positive). Evolution occurred in 22.4% cases when three clinical profiles were analysed and 36.6% considering five clinical profiles. There were no statistically significant differences among the three clinical profiles in overall survival (OS). When five clinical profiles were analysed, HR-negative/HER2-zero had the worst OS with HzR = 6.82 and 95% confidence interval (CI) =1.19, 39.23, P = 0.031. In the multivariable analysis, ER-positive was associated with HER2 discordance less than oestrogen receptor (ER)-negative with odds ratio (OR) = 0.354 and 95% CI = 0.14-0.88, P = 0.025. In the multivariable analysis, patients with Eastern Cooperative Oncology Group 2+ had worse OS with hazard ratio (HzR) = 5.54 and 95% CI = 2.4-12.79, P < 0.0001. HR concordant had better OS with HzR = 0.34 and 95% CI = 0.2-0.63, P = 0.0004. HER2 conversion from low to zero had worse OS than HER2 concordance with HzR 2.66 and 95% CI = 1.21-5.83, P = 0.015.

Conclusions: Five-profile classification provides a more accurate idea about the rate of potential change in treating BC in the metastatic setting.

Keywords: HER2‐low; biomarkers; breast cancer; evolution; metastasis; prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Receptor, ErbB-2* / analysis
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Biomarkers, Tumor
  • Receptor, ErbB-2
  • ERBB2 protein, human
  • Receptors, Estrogen
  • Receptors, Progesterone