posters International Association for Breast Cancer Research 2014

Tumour-infiltrating T cells and RANK/RANKL expression in locally-advanced and metastatic breast cancer (#110)

Elizabeth Thomas 1 2 , Timothy Miller 1 2 , Dawn Farquhar 1 , Kim Cheah 3 , Jiake Xu 4 , Christobel Saunders 1 2 , Nikolajs Zeps 1 2
  1. St John of God Health Care, Subiaco, WA, Australia
  2. School of Surgery, The University of Western Australia , Perth, WA, Australia
  3. Anatomical Pathology, St John of God Pathology, Perth, WA, Australia
  4. School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA, Australia

It is now well accepted that intra- and peri-tumoural infiltration of T cells has prognostic significance in breast cancer. Specifically the current literature indicates that a high FOXP3+ to CD8+ infiltrating T cell ratio is prognostic of poor outcome in breast cancers. However, there is evidence that the prognostic power of T cell infiltration must take into account the specific T cell subsets present in the particular tumour types. RANK is overexpressed in a proportion of breast cancers and this is associated with the more aggressive basal phenotype associated with a poor outcome. In normal breast tissue, RANK signalling activated at the onset of pregnancy by RANK-ligand (RANKL) and/or progestins drives differention of the resting epithelium to produce the fully differentiated lactating gland. This regresses post-lactation and the RANK-positive population remains quiescent unless reactivated in subsequent pregnancies. In prostate it has been shown that FOXP3+ T cells infiltrating the tumour express RANKL and that this is associated with invasion and metastasis. In this study we have used multiplex immunohistochemistry for FOXP3+, CD4+ and CD8+ T cells and RANK+, RANKL+ and PR+ cells,to characterise the T cell subsets in the primary tumour of locally-advanced breast cancer (LABC) and metastatic breast cancer patients with respect to the tumour type. Pilot data indicates there is a strong trend between a high FOXP3+ to CD8+ ratio and poor outcome, irrespective of absolute FOXP3+ cell number. We are currently investigating this in a larger cohort of 300 patients diagnosed with Infiltrating Duct Carcinoma with respect to RANK, RANKL and PR expression.