title: Targeting the programmed cell death-1 pathway in breast and ovarian cancer.
abstract: OBJECTIVE
  Immune checkpoint blockade is changing cancer therapy. Targeting the programmed cell death-1 (PD-1) pathway releases T cells from inhibitory signals within the tumor microenvironment, thereby activating a latent antitumor immune response. Here, we review the biology underlying the activity of PD-1/programmed cell death-ligand 1 (PD-L1) antagonists, and data describing their clinical activity in breast and ovarian cancer.
  
  
  RESULTS
  Several antagonists of PD-1 and PD-L1 have been tested in breast and ovarian cancer. These drugs are generally well tolerated, with some immune-related adverse events that are typically easily managed. Objective response rates generally range from about 10 to 20% in both breast cancer and ovarian cancer, with durable responses noted in multiple trials. Selecting patients with PD-L1 expression by cells within the tumor microenvironment appears to enrich for responses. These agents are under accelerated development based on these promising early data.
  
  
  CONCLUSIONS
  Monoclonal antibody-based blockade of the PD-1 pathway results in objective and durable clinical responses in a subset of patients with breast or ovarian cancers, particularly those with PD-L1-positive cells within the tumor microenvironment. Current priorities are to refine biomarkers of therapeutic response, and to develop combination immunotherapy strategies that integrate PD-1/PD-L1 antagonists with both standard and immune-based cancer therapies to increase efficacy.
authors.affiliation: aDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA bThe Netherlands Cancer Institute, Amsterdam, the Netherlands cThe Kelly Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Leisha A
authors.initials: LA
authors.lastname: Emens
authors.forename: Marleen
authors.initials: M
authors.lastname: Kok
authors.forename: Laureen S
authors.initials: LS
authors.lastname: Ojalvo
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen