Association of IL-8 and eNOS polymorphisms with clinical outcomes in bevacizumab-treated breast cancer patients: an exploratory analysis

Clin Transl Oncol. 2016 Jan;18(1):40-6. doi: 10.1007/s12094-015-1334-7. Epub 2015 Jul 4.

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.

Patients and 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.

Conclusion: 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.

Keywords: Bevacizumab; IL-8; Resistance; SNPs; eNOS.

MeSH terms

  • Adult
  • Aged
  • Bevacizumab / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Female
  • Genetic Association Studies
  • Humans
  • Interleukin-8 / genetics*
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Interleukin-8
  • Bevacizumab
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III