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


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.
Font
A
A
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona. Electronic address: afont@ico.scs.es.
Taron
M
M
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona; Pangaea Biotech, USP Dexeus University Institute, Barcelona.
Gago
J L
JL
Urology Service, Department of Surgery, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona.
Costa
C
C
Pangaea Biotech, USP Dexeus University Institute, Barcelona.
Sánchez
J J
JJ
Autonomous University of Madrid, Madrid.
Carrato
C
C
Pathology Service, Hospital Germans Trias I Pujol, Badalona, Spain.
Mora
M
M
Urology Service, Department of Surgery, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona.
Celiz
P
P
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona.
Perez
L
L
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona.
Rodríguez
D
D
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona.
Gimenez-Capitan
A
A
Pangaea Biotech, USP Dexeus University Institute, Barcelona.
Quiroga
V
V
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona.
Benlloch
S
S
Pangaea Biotech, USP Dexeus University Institute, Barcelona.
Ibarz
L
L
Urology Service, Department of Surgery, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona.
Rosell
R
R
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona; Pangaea Biotech, USP Dexeus University Institute, Barcelona.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D014747:Vinblastine / Q000008:administration & dosage
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D012333:RNA, Messenger; D014747:Vinblastine; D002945:Cisplatin; D008727:Methotrexate