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

Author

Ettore Capoluongo, Carlo Barone, Concetta Santonocito, Antonia Strippoli, M. Di Salvatore, S. Cappuccio, Alessandra Cassano, P. Fuso, Giulia Nazzicone, Armando Orlandi, Antonio Astone, L. lo Giudice, Ernesto Rossi, Alessandro Inno, M. G. Rodriquenz, Di Salvatore, M, Lo Giudice, L, Rossi, E, Santonocito, C, Nazzicone, G, Rodriquenz, Mg, Cappuccio, S, Inno, A, Fuso, P, Orlandi, A, Strippoli, A, Capoluongo, E, Astone, A, Cassano, A, and Barone, C

Subjects
Adult, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Pathology, Nitric Oxide Synthase Type III, Bevacizumab, medicine.medical_treatment, Resistance, Breast Neoplasms, Polymorphism, Single Nucleotide, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Enos, Internal medicine, Genotype, medicine, Humans, Interleukin 8, Genetic Association Studies, Aged, Retrospective Studies, Chemotherapy, Settore MED/06 - ONCOLOGIA MEDICA, biology, IL-8, business.industry, Interleukin-8, General Medicine, Middle Aged, SNPs, eNOS, Prognosis, medicine.disease, biology.organism_classification, Metastatic breast cancer, Clinical trial, Treatment Outcome, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Female, business, Polymorphism, Restriction Fragment Length, medicine.drug
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.

Published
2016

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