1661P - The predictive role of the 53BP1 pathway in advanced non-small-cell lung cancer (NSCLC) patients (P) treated with first-line platinum-based chemothe...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Laura Bonanno
Authors L. Bonanno1, C. Costa2, M. Majem3, A. Gimenez-Capitan2, I. Rodriguez4, J.J. Sánchez5, B. Massuti Sureda6, A. Favaretto7, M. Rugge8, R. Rosell9
  • 1U.o. C. Oncologia Medica 2, Istituto Oncologico Veneto IOV-IRCCS, IT-35128 - Padova/IT
  • 2Laboratoy Of Biology Department, Pangaea Biotech, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 3Oncology, Hospital de Sant Pau, 08025 - Barcelona/ES
  • 4Statistics, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 5Statistics, Autonomous University of Madrid, 28029 - Madrid/ES
  • 6Medical Oncology, Hospital General Universitario de Alicante, ES-03010 - Alicante/ES
  • 7U.o.oncologia Medica, Istituto Oncologico Veneto IOV-IRCCS, IT-35128 - Padova/IT
  • 8Pathology And Cytopathology Unit, University of Padova, 35137 - Padova/IT
  • 9Medical Oncology Service, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, 08916 - Badalona/ES

Abstract

Background

Preclinical and clinical data have shown that low BRCA1 expression increases sensitivity to platinum. However, the complexity of DNA repair pathways suggests that the BRCA1 function could be modulated by several proteins. MDC1, the protein initiating the response to DNA double strand breaks, activates two parallel pathways: 53BP1 and BRCA1. We hypothesized that the mRNA expression of components involved in the 53BP1 pathway could influence the predictive value of BRCA1.

Methods

mRNA expression levels of BRCA1, MDC1, UBC13, RNF8, 53BP1, PIAS4, MMSET and UBC9 were assessed by real-time PCR analysis in 115 paraffin-embedded tumor samples collected from advanced NSCLC p treated with first-line platinum-based chemotherapy without taxanes.

Results

Expression levels of BRCA1 were correlated with MDC1 (&rgr; = 0.47, P < 0.0001), UBC13 (&rgr; = 0.41, P = 0.001), RNF8 (&rgr; = 0.41, P = 0.001), 53BP1 (&rgr; = 0.37, P = 0.003), PIAS4 (&rgr; = 0.51, P < 0.0001), MMSET (&rgr; = 0.57, P < 0.0001) and UBC9 (&rgr; = 0.31,P = 0.01). Median overall survival (OS) was 11 months (m), and progression-free survival (PFS) was 7 m. Among p with low levels of BRCA1, median OS was 19.3 m and PFS was 10 m for p with low levels of 53BP1, compared to 8.2 m and 5.9 m, respectively, for p with high levels of 53BP1 (OS: P = 0.01; PFS: P < 0.0001). Among p with high levels of BRCA1, no significant differences in OS were observed according to 53BP1 expression levels.

Conclusions

Advanced NSCLC p with low levels of both BRCA1 and 53BP1 showed significantly improved outcome to first-line platinum-based chemotherapy. The assessment of BRCA1 and 53BP1 can be useful for customizing chemotherapy.

Disclosure

All authors have declared no conflicts of interest.