title: Association of IL-8 and eNOS polymorphisms with clinical outcomes in bevacizumab-treated breast cancer patients: an exploratory analysis.
abstract: BACKGROUND
  The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients.
  
  
  METHODS
  eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed.
  
  
  RESULTS
  Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed.
  
  
  CONCLUSIONS
  These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials.
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy. disalvatore.mariantonietta@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Di Salvatore
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Lo Giudice
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Rossi
authors.affiliation: Laboratory of Clinical Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Santonocito
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Nazzicone
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Rodriquenz
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cappuccio
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.|Medical Oncology, Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni 5, 37024, Negrar, VR, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Inno
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Fuso
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Strippoli
authors.affiliation: Laboratory of Clinical Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Capoluongo
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Astone
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cassano
authors.affiliation: Unit of Clinical Oncology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Barone
mesh_terms: D000328:Adult; D000368:Aged; D000068258:Bevacizumab / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D016209:Interleukin-8; D000068258:Bevacizumab; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Bevacizumab; IL-8; Resistance; SNPs; eNOS