title: Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Rhiannon K
authors.initials: RK
authors.lastname: Beckers
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Selinger
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vilain
authors.affiliation: Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Madore
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: James S
authors.initials: JS
authors.lastname: Wilmott
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.|The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Harvey
authors.affiliation: The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Holliday
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Cooper
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Robbins
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|The Strathfield Breast Centre, Strathfield, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Gillett
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|The Strathfield Breast Centre, Strathfield, NSW, Australia.
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Kennedy
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|The Strathfield Breast Centre, Strathfield, NSW, Australia.|Department of Breast and Endocrine Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gluch
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|The Strathfield Breast Centre, Strathfield, NSW, Australia.|Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Hugh
authors.initials: H
authors.lastname: Carmalt
authors.affiliation: Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Cindy
authors.initials: C
authors.lastname: Mak
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.|Department of Surgery, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Warrier
authors.affiliation: Department of Radiation Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.|Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
authors.forename: Harriet E
authors.initials: HE
authors.lastname: Gee
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Anatomical Pathology Department, Concord Repatriation General Hospital, Concord, NSW, Australia.
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: McLean
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Emily
authors.initials: E
authors.lastname: Walker
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
authors.forename: Catriona M
authors.initials: CM
authors.lastname: McNeil
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Beith
authors.affiliation: The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, NSW, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Swarbrick
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, NSW, Australia.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: PDL1; triple-negative breast cancer; tumour-infiltrating lymphocytes