Discordance between PAM50 intrinsic subtyping and immunohistochemistry in South African women with breast cancer

Breast Cancer Res Treat. 2023 May;199(1):1-12. doi: 10.1007/s10549-023-06886-3. Epub 2023 Mar 3.

Abstract

Purpose: Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment.

Methods: In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay.

Results: IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the lowest concordance. By altering the cutoff for Ki67, and realigning the HER2/ER/PR-positive patients to IHC-HER2, we improved concordance with the intrinsic subtypes.

Conclusion: We suggest that the Ki67 be changed to a cutoff of 20-25% in our population to better reflect the luminal subtype classifications. This change would inform treatment options for breast cancer patients in settings where genomic assays are unaffordable.

Keywords: Breast cancer; Immunohistochemistry; PAM50; Sub-Saharan Africa; Subtypes.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / genetics
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • South Africa / epidemiology

Substances

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