Abstract
BackgroundThe molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast cancer susceptibility gene 1 (BRCA1) expression has been found to switch the response to cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer.Patients and MethodsQuantitative real-time polymerase chain reaction (qPCR) was performed to examine BRCA1 mRNA expressions in paraffin-embedded specimens from 144 patients with advanced or metastatic esophageal squamous cell carcinoma who received cisplatin- or docetaxel-based first-line treatments.ResultsLow BRCA1 mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively) and median overall survival (mOS; P = 0.002 and P<0.001, respectively) in cisplatin-based chemotherapy or chemoradiotherapy group and also correlated with decreased RR (P = 0.017 and 0.024, respectively) and mOS (both P<0.001) in docetaxel-based chemotherapy or chemoradiotherapy group. Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12–0.71; P = 0.007) or chemoradiotherapy (HR 0.12; 95%CI 0.04–0.37; P<0.001) group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05–12.28; P<0.001) or chemoradiotherapy (HR 7.02; 95%CI 2.37–27.77; P<0.001) group.ConclusionsBRCA1 mRNA expression could be used as a predictive and prognostic marker in esophageal cancer who underwent first-line cisplatin- or docetaxel-based treatments.
Highlights
Esophageal cancer, as the sixth most common cause of cancer death in the world, lead to 407,000 deaths estimated in 2008 [1]
Low Breast cancer susceptibility gene 1 (BRCA1) mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively) and median overall survival in cisplatin-based chemotherapy or chemoradiotherapy group and correlated with decreased RR (P = 0.017 and 0.024, respectively) and mOS in docetaxel-based chemotherapy or chemoradiotherapy group
Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12–0.71; P = 0.007) or chemoradiotherapy (HR 0.12; 95%CI 0.04–0.37; P,0.001) group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05– 12.28; P,0.001) or chemoradiotherapy (HR 7.02; 95%CI 2.37–27.77; P,0.001) group
Summary
Esophageal cancer, as the sixth most common cause of cancer death in the world, lead to 407,000 deaths estimated in 2008 [1]. Some molecular markers have been identified for tailored treatment of esophageal cancer, including platinum related markers [glutathione S-transferase p (GST-p), excision repair cross-complementing 1 (ERCC1) and p-glycoprotein (Pgp)], 5-FU related markers [thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD)] and some proteins in various DNA repair pathways [7,8,9]. These studies mostly focused on the personalized therapies of 5-Fu or/and cisplatin-based treatments. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer
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