BRCA1 mRNA expression and outcome to neoadjuvant cisplatin-based chemotherapy in bladder cancer

A. Font, M. Taron, J. L. Gago, C. Costa, J. J. Sánchez, C. Carrato, M. Mora, P. Celiz, L. Perez, D. Rodríguez, A. Gimenez-Capitan, V. Quiroga, S. Benlloch, L. Ibarz, R. Rosell

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Abstract

Background: Neoadjuvant chemotherapy has shown a modest benefit in muscle-invasive bladder cancer patients; however, the subset of patients most likely to benefit has not been identified. BRCA1 plays a central role in DNA repair pathways and low BRCA1 expression has been associated with sensitivity to cisplatin and longer survival in lung and ovarian cancer patients. Patients and methods: We assessed BRCA1 messenger RNA expression levels in paraffin-embedded pre-treatment tumor samples obtained by transurethral resection from 57 patients with locally advanced bladder cancer subsequently treated with neoadjuvant cisplatin-based chemotherapy. BRCA1 levels were divided into terciles and correlated with pathological response and survival. Results: A significant pathological response (pT0-1) was attained in 66% (24 of 39) of patients with low/intermediate BRCA1 levels compared with 22% (4 of 18) of patients with high BRCA1 levels (P = 0.01). Median survival was 168 months in patients with low/intermediate levels and 34 months in patients with high BRCA1 levels (P = 0.002). In the multivariate analysis for survival, only BRCA1 expression levels and lymphovascular invasion emerged as independent prognostic factors. Conclusions: Our data suggest that BRCA1 expression may predict the efficacy of cisplatin-based neoadjuvant chemotherapy and may help to customize therapy in bladder cancer patients. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Original languageEnglish
Pages (from-to)139-144
JournalAnnals of Oncology
Volume22
Issue number1
DOIs
Publication statusPublished - 1 Jan 2011

Keywords

  • Bladder cancer
  • BRCA1 mRNA expression
  • Cisplatin
  • Customized chemotherapy
  • Pathological response
  • Prognostic marker

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    Font, A., Taron, M., Gago, J. L., Costa, C., Sánchez, J. J., Carrato, C., Mora, M., Celiz, P., Perez, L., Rodríguez, D., Gimenez-Capitan, A., Quiroga, V., Benlloch, S., Ibarz, L., & Rosell, R. (2011). BRCA1 mRNA expression and outcome to neoadjuvant cisplatin-based chemotherapy in bladder cancer. Annals of Oncology, 22(1), 139-144. https://doi.org/10.1093/annonc/mdq333