Abstract 44P
Background
Metaplastic breast cancer (MBC) is a chemotherapy-resistant and rare breast cancer (BC) subtype. Studies have shown that MBC may exhibit higher levels of PD-L1, and FOXP3 could be a possible marker for regulatory T cells. Despite the associations of ALK rearrangements and BRAF mutations with aggressive breast cancer subtypes, their exploration in MBC remains limited. This study aimed to investigate PD-L1, FOXP3, EML4-ALK fusion protein, and BRAFV600E mutation expression in MBC specimens.
Methods
We retrospectively studied MBC cases diagnosed at the University General Hospital of Ioannina's Pathology Department from 2005 to 2021, following institutional approval. Among the 22 identified cases, one was excluded due to a lack of formalin-fixed paraffin (FFP) tissue blocks. Clinicopathological data were extracted from the records of the remaining twenty-one cases. MBC classification adhered to WHO guidelines, utilizing immunohistochemistry for ER, PR, HER2 status, BRAFV600E mutation, EML4-ALK fusion protein, FOXP3, and PD-L1 expression in FFP tissues per literature guidelines.
Results
Patients had a median age of 74 years. The predominant histological types were squamous carcinoma (14.3%), mixed (71.4%), adenosquamous (9.5%), and one case of breast carcinosarcoma. Additionally, 47.6% had an H score ≥ 1 for ER, 33.3% for PR, 14.3% with HER2 3+, with all MBCs showing high proliferation (Ki67%>40%). Notably, no BRAF mutations were found, and only 2 patients had moderate ALK staining. PD-L1 expression in tumor cells was positive (≥ 1%) in 42.9%, while 85% showed positive PD-L1 expression in tumor-infiltrating lymphocytes (TILs). FOXP3 nuclear expression in tumor cells was absent in all MBC tissues, with 100% showing low infiltration in tumor cells (cytoplasmic staining) and 52.4% displaying high infiltration in immune cells (nuclear staining in lymphocytes).
Conclusions
This study enhances our understanding of MBC's molecular and immune profile, marking the initial exploration of ALK overexpression and BRAFV600E mutation, both found to be absent. Our findings confirm MBC as a distinct BC subtype with elevated PD-L1 expression in tumor cells and TILs. This supports the rationale for incorporating immunotherapy in MBC management.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.