title: Immune profiles of elderly breast cancer patients are altered by chemotherapy and relate to clinical frailty.
abstract: Effective therapeutic management of elderly patients with cancer, on an individual basis, remains a clinical challenge. Here, we identify novel biomarkers to assess elderly patients (≥70 years of age) with breast cancer undergoing treatment with or without chemotherapy.
  
  
  
  We performed comprehensive geriatric assessment and measured markers sensitive to alteration in ageing, including leukocyte telomere length, CMV serostatus, levels of circulating growth factors and cytokines, and immune profiling of T cell and myeloid populations in blood before and at 3 months and 12 months after initiation of therapy, using flow cytometry.
  
  
  
  We observed changes in immune profiles over time that were specific to patients receiving chemotherapy; these patients had elevated CD4+ T effector memory re-expressing CD45RA (TEMRA) cells and relatively lower CD8+ central memory cells at 3 months, with normalized levels after 12 months. Patients' baseline immune profiles correlated with markers such as telomere length, cytomegalovirus (CMV) serostatus and levels of circulating cytokines. We also identified correlations between baseline immune profile and geriatric assessment, i.e. more frail patients had higher levels of granulocytic cells but lower levels of cells with suppressor phenotypes including myeloid-derived suppressor cells and regulatory T cells, although none of the examined immune populations correlated with chronological age. Importantly, immune profiles prior to therapy predicted unexpected hospitalizations in patients receiving chemotherapy.
  
  
  
  These findings suggest that immune profiling may represent a novel complementary approach to more accurately assess the global health status of the elderly patient with breast cancer and select the most appropriate individual treatment option.
  
  
  
  ClinicalTrials.gov, NCT00849758 . Registered on 20 February 2009.
authors.affiliation: Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany.|Present: Yale Cancer Center, Yale University School of Medicine, New Haven, 06510, CT, USA.
authors.forename: Jithendra Kini
authors.initials: JK
authors.lastname: Bailur
authors.affiliation: Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium.|Department of General Medical Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hatse
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium.|Department of General Medical Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brouwers
authors.affiliation: Leuven Multidisciplinary Breast Center, University Hospital Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Smeets
authors.affiliation: Leuven Multidisciplinary Breast Center, University Hospital Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.affiliation: Interuniversity Center for Biostatistics and Statistical Bioinformatics, Leuven, Belgium.
authors.forename: Annouschka
authors.initials: A
authors.lastname: Laenen
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium.|Department of General Medical Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium.|Leuven Multidisciplinary Breast Center, University Hospital Leuven, Leuven, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
authors.affiliation: Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany. mrchristophershipp@gmail.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Shipp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000209:etiology; D005260:Female; D016330:Frail Elderly; D015577:Geriatric Assessment; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D016130:Immunophenotyping; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016615:Telomere
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Blood leukocyte; Breast cancer; Chemotherapy; Clinical frailty; Immune profile