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

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. [ABSTRACT FROM AUTHOR]