The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer
Por:
Margeli, M, Cirauqui, B, Castella, E, Tapia, G, Costa, C, Gimenez-Capitan, A, Barnadas, A, Ronco, MS, Benlloch, S, Taron, M and Rosell, R
Publicada:
3 mar 2010
Resumen:
Background: A fraction of sporadic breast cancers has low BRCA1 expression. BRCA1 mutation carriers are more likely to achieve a pathological complete response with DNA-damage-based chemotherapy compared to non-mutation carriers. Furthermore, sporadic ovarian cancer patients with low levels of BRCA1 mRNA have longer survival following platinum-based chemotherapy than patients with high levels of BRCA1 mRNA.
Methodology/Principal Findings: Tumor biopsies were obtained from 86 breast cancer patients who were candidates for neoadjuvant chemotherapy, treated with four cycles of neoadjuvant fluorouracil, epirubicin and cyclophosphamide. Estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 and vimentin were examined by tissue microarray. HER2 were also assessed by chromogenic in situ hybridization, and BRCA1 mRNA was analyzed in a subset of 41 patients for whom sufficient tumor tissue was available by real-time quantitative PCR. Median time to progression was 42 months and overall survival was 55 months. In the multivariate analysis for time to progression and overall survival for 41 patients in whom BRCA1 could be assessed, low levels of BRCA1 mRNA, positive PR and negative lymph node involvement predicted a significantly lower risk of relapse, low levels of BRCA1 mRNA and positive PR were the only variables associated with significantly longer survival.
Conclusions/Significance: We provide evidence for a major role for BRCA1 mRNA expression as a marker of time to progression and overall survival in sporadic breast cancers treated with anthracycline-based chemotherapy. These findings can be useful for customizing chemotherapy.
Filiaciones:
:
Hosp Badalona Germans Trias & Pujol, Dept Med, Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain
Autonomous Univ Barcelona, Badalona, Spain
:
Hosp Badalona Germans Trias & Pujol, Dept Med, Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain
Autonomous Univ Barcelona, Badalona, Spain
Castella, E:
Hosp Badalona Germans Trias & Pujol, Pathol Serv, Badalona, Spain
:
Hosp Badalona Germans Trias & Pujol, Pathol Serv, Badalona, Spain
Costa, C:
USP Dexeus Univ Inst, Pangaea Biotech SA, Barcelona, Spain
Gimenez-Capitan, A:
USP Dexeus Univ Inst, Pangaea Biotech SA, Barcelona, Spain
Barnadas, A:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Ronco, MS:
Univ Alcala de Henares, Madrid, Spain
Benlloch, S:
USP Dexeus Univ Inst, Pangaea Biotech SA, Barcelona, Spain
Taron, M:
Hosp Badalona Germans Trias & Pujol, Dept Med, Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain
Autonomous Univ Barcelona, Badalona, Spain
USP Dexeus Univ Inst, Pangaea Biotech SA, Barcelona, Spain
:
Hosp Badalona Germans Trias & Pujol, Dept Med, Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain
Autonomous Univ Barcelona, Badalona, Spain
USP Dexeus Univ Inst, Pangaea Biotech SA, Barcelona, Spain
Green Submitted, gold, Green Published
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