title: Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors.
abstract: BACKGROUND
  Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors.
  
  
  METHODS
  Data from consecutive breast cancer patients receiving chemotherapy with 4-6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles.
  
  
  RESULTS
  Overall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR = 0.78 [0.65; 0.93]) and haemoglobin (OR = 0.81 [0.67; 0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR = 6.7 [1.04; 43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR = 1.02 [1.01; 1.03]), carriers of the rs246221 variant C-allele (OR = 2.0 [1.03; 3.86]) in MRP1 and the rs351855 variant C-allele (OR = 2.48 [1.13; 5.44]) in FGFR4. Lower height (OR = 0.62 [0.41; 0.92]) increased risk of FN in the first cycle.
  
  
  CONCLUSIONS
  Both established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings.
authors.forename: Alena M
authors.initials: AM
authors.lastname: Pfeil
authors.forename: Christof
authors.initials: C
authors.lastname: Vulsteke
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Dieudonné
authors.forename: Ruth
authors.initials: R
authors.lastname: Pettengell
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hatse
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Szucs
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwenkglenks
authors.affiliation: Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. hans.wildiers@uzleuven.be.
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D042241:Early Diagnosis; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents