TROP2, androgen receptor, and PD-L1 status in histological subtypes of high-grade metaplastic breast carcinomas

Histopathology. 2023 Apr;82(5):664-671. doi: 10.1111/his.14852. Epub 2023 Jan 9.

Abstract

Aims: High-grade metaplastic breast carcinoma (HG-MBC) is a rare subtype of invasive breast carcinoma, mostly triple-negative. Metaplastic carcinomas are less responsive to neoadjuvant chemotherapy and are associated with a worse outcome than invasive carcinomas of no special type.

Methods: Clinicopathological characteristics and immunophenotype were retrospectively assessed in a series of 65 patients diagnosed with HG-MBC between 2005 and 2017 at the Curie Institute (antibody panel: oestrogen receptor [ER], progesterone receptor [PR], androgen receptor [AR], human epidermal growth factor receptor 2 [HER2], programmed death ligand-1 [PD-L1], and trophoblast cell surface antigen 2 [TROP2]).

Results: The median age at diagnosis was 59.5 years. Six (9%) patients had metastatic disease at diagnosis. Among the nonmetastatic patients receiving neoadjuvant therapy, 26% (5/19) achieved pathological complete response. Most tumours were pT1/pT2 (77%) and 12% were pN+. Histological subtypes (mixed, squamous, mesenchymal, and spindle cell) were 40%, 35.5%, 15.5%, and 9%, respectively. Tumour-infiltrating lymphocytes were low or moderate except when squamous differentiation was present. Most tumours were triple-negative (92%). AR and TROP2 were positive in 34% and 85% of the cases, respectively. PD-L1 was positive in tumour cells in 18% (cutoff: 1% of positive tumour cells) of the cases and in tumour-infiltrating immune cells in 40% (cutoff: 1% of tumour area) of the cases. Notably, spindle cell and mesenchymal metaplastic breast carcinomas were mostly PDL1-negative. Lastly, 21 (32.3%) cases were HER2-low, all being HER2 1+, with no HER2 2+.

Conclusion: Metaplastic breast carcinoma could benefit from tailored therapeutic strategies adapted to the phenotypic specificities of histological subtypes.

Keywords: High-grade metaplastic breast carcinoma; clinicopathological characteristics; histological subtypes; immunophenotype; theranostic markers.

MeSH terms

  • B7-H1 Antigen / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / pathology
  • Carcinoma, Squamous Cell*
  • Female
  • Humans
  • Middle Aged
  • Receptor, ErbB-2 / metabolism
  • Receptors, Androgen
  • Retrospective Studies

Substances

  • CD274 protein, human
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • Receptors, Androgen
  • Receptor, ErbB-2