Poster Presentation 31st Lorne Cancer Conference 2019

The tumour immune microenvironment in metaplastic breast cancer (#211)

Emarene Kalaw 1 , Amy McCart Reed 1 , Lucinda Taege 2 , Malcolm Lim 1 , Kate Johnstone 2 , Jamie Kutasovic 1 , Jodi Saunus 1 , Colleen Niland 1 , Kaltin Ferguson 1 , Irma Gresshoff 1 , Ashwini Raghavendra 1 , Kate Harvey 3 , Caroline Cooper 3 , Nirmala Pathmanathan 4 , Gary Tse 5 , David Papadimos 6 , Rajadurai Pathmanathan 7 , Gavin Harris 8 , Rin Yamaguchi 9 , Puay Hoon Tan 10 , Stephen Fox 11 , Sandra O'Toole 3 , Peter Simpson 1 , Sunil Lakhani 1 2
  1. Faculty of Medicine, University of Queensland Centre for Clinical Research, Herston, 4029, QLD, Australia
  2. Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
  3. Garvan Institute of Medical Research and the Kinghorn Cancer Centre, Darlinghust, NSW, Australia
  4. Westmead Breast Cancer Institute, University of Sydney, Sydney, NSW, Australia
  5. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Hongkong
  6. Department of Histopathology, Sullivan Nicolaides Pathology, Bowen Hills, QLD, Australia
  7. Sime Darby Medical Centre, Selangor, Selangor, 47500 , Malaysia
  8. Dept of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
  9. Department of Pathology and Laboratory Medicine, Kurume University Medical Center, 155-1 Kokubu, Kurume‐shi 839‐0863, Japan
  10. Division of Pathology, Singapore General Hospital, Singapore
  11. Peter MacCallum Cancer Centre, Melbourne, Australia

INTRODUCTION: Metaplastic breast carcinoma (MBC) encompasses a heterogeneous group of tumours that differentiates into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements 1. Tumour cells and other cells in the tumour microenvironment express Program Death Ligand 1 (PD-L1); a novel therapeutic target. Activation of PD-1/PD-L1 pathway in neoplastic cells results in down-regulation of the immune response and cancer cell survival. Forkhead box P3 (FOXP3) is a marker of regulatory T cells (Tregs) which are a component of the Tumour infiltrating lymphocytes (TILS) that can elicit a pro-tumour immune response 2. PDL-1 expression and relevance of TILS in MBC is not yet known. METHODS: Quantification of TILS and expression of PD-L1 and FOXP3 were evaluated on a large cohort. PDL-1 expression was investigated in the tumour area and TILS expressing PD-L1 in the stroma (sTILS) were also assessed. Absolute count of FOXP3 was scored on both the intratumoural (iTILS) and stromal (sTILS). Histologic score (H-score) of both PD-L1 and FOXP3 was generated. RESULTS: Low tumour and high sTILS PD-L1 expression displayed the best clinical outcome. FOXP3 iTILS is associated with adverse prognostic outcome. CONCLUSIONS: We report the biological significance of TILS in a rare and aggressive form of breast cancer; wherein its presence establishes a potential prognostic value. A subset of patients would likely respond to anti-PD-1/PD-L1 therapy. Our findings support the concept that MBC is immunogenic, and suggest the role of immune-based therapies in MBC patients.

 

 

 

  1. 1.Lakhani S. WHO Classification of Tumours of the Breast 2012. 2.Dushyanthen S, Beavis P, Loi S et al. Relevance of Tumour infiltrating lymphocytes in breast cancer. BioMed Central Medicine. 2015; 13:202.