title: PD-L1 expression and tumor infiltrating PD-1+ lymphocytes associated with outcome in HER2+ breast cancer patients.
abstract: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes. Also, we evaluate the relationship of PD-1 TIL and PD-L1 expression with patients' survival, particularly for breast cancers with high TIL.
  
  
  
  Immunohistochemical analysis of PD-L1 on tissue arrays for 1091 breast cancer patients and PD-1 TIL on 97 whole sections was performed. Associations of PD-L1 with luminal cancers (p < 0.001) and features associated with that subtype [lower histologic grade, absence of necrosis, ER, PR, and AR expression (p < 0.001)] were observed. However, in HER2+ breast cancers, PD-L1 was an independent poor prognostic indicator (DFS: HR = 1.866, p = 0.001; OS: HR = 1.517, p = 0.036). Interestingly, HER2+ cancers showed a lower PD-1 TIL level compared to the other high TIL cases (p = 0.011). Cases with low PD-TIL but high PD-L1 expression showed the worst survival. This could be indicative of an active immune suppression by PD-L1 expression.
  
  
  
  Our data showed the relevance of PD-L1 expression in HER2+ breast cancer. A combined evaluation of PD-L1 and PD-1 TIL in the prognosis of breast cancer might also be of value in treatment prediction.
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong.
authors.forename: Julia Y S
authors.initials: JY
authors.lastname: Tsang
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong.
authors.forename: Wai-Ling
authors.initials: WL
authors.lastname: Au
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong.
authors.forename: Kwan-Yin
authors.initials: KY
authors.lastname: Lo
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong.
authors.forename: Yun-Bi
authors.initials: YB
authors.lastname: Ni
authors.affiliation: Department of Anatomic Pathology, Centro Hospitalar Conde de Sao Januario, Macao SAR, China.
authors.forename: Thazin
authors.initials: T
authors.lastname: Hlaing
authors.affiliation: Department of Pathology, Shenzhen People's Hospital, Shenzhen, 518020, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology, Kwong Wah Hospital, Yau Ma Tei, Hong Kong.
authors.forename: Siu-Ki
authors.initials: SK
authors.lastname: Chan
authors.affiliation: Department of Pathology, Tuen Mun Hospital, Tuen Mun, Hong Kong.
authors.forename: Kui-Fat
authors.initials: KF
authors.lastname: Chan
authors.affiliation: Department of Pathology, Tuen Mun Hospital, Tuen Mun, Hong Kong.
authors.forename: Sai-Yin
authors.initials: SY
authors.lastname: Cheung
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong. garytse@cuhk.edu.hk.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Tse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; D061026:Programmed Cell Death 1 Receptor; D018719:Erb-b2 Receptor Tyrosine Kinases; C423236:CD274 protein, human
keywords: Breast cancer subtype; Human epidermal growth factor receptor 2; Immunohistochemistry; Programmed death ligand 1; Tumor infiltrating lymphocyte