Assessment of Predictive Biomarkers in Breast Cancer: Challenges and Updates

Pathobiology. 2022;89(5):263-277. doi: 10.1159/000525092. Epub 2022 Jun 21.

Abstract

The management of patients with breast cancer (BC) relies on the assessment of a defined set of well-established prognostic and predictive markers. Despite overlap, prognostic markers are used to assess the risk of recurrence and the likely benefit of systemic therapy, whereas predictive markers are used to determine the type of systemic therapy to be offered to an individual patient. In this review, we provide an update and present some challenges in the assessment of the main BC-specific molecular predictive markers, namely hormone receptors (oestrogen receptor [ER] and progesterone receptor [PR]), human epidermal growth factor receptor 2 (HER2), and KI67. As the main platform for assessing these markers in BC is immunohistochemistry (IHC), we address the cut-off values used to define positivity, the ER-low subgroup, the existence and significance of the ER-/PR+ phenotype, the use of PR in routine practice, and the role of hormone receptors in ductal carcinoma in situ. We discuss the newly introduced HER2-low class of BC and the clinical/biological difference between different HER2 groups (e.g., HER2 IHC score 3+ BCs vs. those with a HER2 IHC score 2+ with HER2 gene amplification). The review concludes with an update on the applications of KI67 assessment in BC and observations on the role of immune checkpoint identification in BC.

Keywords: Breast cancer; HER2; Immunohistochemistry; Ki67; Oestrogen receptor; Predictive markers; Progesterone receptor.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Female
  • Hormones
  • Humans
  • Ki-67 Antigen / genetics
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone* / genetics
  • Receptors, Progesterone* / metabolism

Substances

  • Biomarkers, Tumor
  • Hormones
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2