Rhiannon K Beckers1, Christina I Selinger1, Ricardo Vilain1,2,3, Jason Madore3, James S Wilmott2,3, Kate Harvey1,4, Anne Holliday4, Caroline L Cooper1,2, Elizabeth Robbins1, David Gillett2,5, Catherine W Kennedy2,5, Laurence Gluch2,5,6, Hugh Carmalt2,5,7, Cindy Mak7, Sanjay Warrier2,7,8, Harriet E Gee9,10, Charles Chan2,11, Anna McLean2, Emily Walker2, Catriona M McNeil2,12, Jane M Beith2,12, Alexander Swarbrick4,13, Richard A Scolyer1,2,3, Sandra A O'Toole1,2,4,13. 1. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 2. Sydney Medical School, University of Sydney, Sydney, NSW, Australia. 3. Melanoma Institute Australia, Sydney, NSW, Australia. 4. The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. 5. The Strathfield Breast Centre, Strathfield, NSW, Australia. 6. Department of Breast and Endocrine Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia. 7. Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 8. Department of Surgery, Prince of Wales Hospital, Randwick, NSW, Australia. 9. Department of Radiation Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 10. Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. 11. Anatomical Pathology Department, Concord Repatriation General Hospital, Concord, NSW, Australia. 12. Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia. 13. St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, NSW, Australia.
Abstract
AIMS: Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC. METHODS AND RESULTS: PDL1 immunohistochemistry was performed on 161 primary TNBCs and assessed in the tumour as well as immune cells in the stromal compartment. PDL1 expression was very common in TNBC, expressed in the tumour cell membrane (64%), cytoplasm (80%) and stromal (93%) cellular compartments. Cytoplasmic tumoral expression of PDL1 was associated with a lower risk of breast cancer-specific death [hazard ratio (HR) 0.45, P = 0.035] while stromal PDL1 expression was associated with a lower rate of deaths from all causes (HR 0.305, P = 0.0042). Membranous expression of PDL1 was not associated with outcome. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only lymphovascular invasion and high tumour-infiltrating lymphocytes were independently prognostic for breast cancer-specific death. CONCLUSION: While PDL1 expression is frequent in TNBC, it was not independently prognostic. There were differences in outcome depending on the cellular compartment of PDL1 expression. These data provide further impetus for investigating the utility of immune checkpoint therapies in TNBC, given the clinical significance of tumour-infiltrating lymphocytes (TILs) and PDL1 expression in this cohort.
AIMS: Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoralPDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC. METHODS AND RESULTS:PDL1 immunohistochemistry was performed on 161 primary TNBCs and assessed in the tumour as well as immune cells in the stromal compartment. PDL1 expression was very common in TNBC, expressed in the tumour cell membrane (64%), cytoplasm (80%) and stromal (93%) cellular compartments. Cytoplasmic tumoral expression of PDL1 was associated with a lower risk of breast cancer-specific death [hazard ratio (HR) 0.45, P = 0.035] while stromal PDL1 expression was associated with a lower rate of deaths from all causes (HR 0.305, P = 0.0042). Membranous expression of PDL1 was not associated with outcome. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only lymphovascular invasion and high tumour-infiltrating lymphocytes were independently prognostic for breast cancer-specific death. CONCLUSION: While PDL1 expression is frequent in TNBC, it was not independently prognostic. There were differences in outcome depending on the cellular compartment of PDL1 expression. These data provide further impetus for investigating the utility of immune checkpoint therapies in TNBC, given the clinical significance of tumour-infiltrating lymphocytes (TILs) and PDL1 expression in this cohort.
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