Zhen Jia

ERCC2 Lys751Gln polymorphism is associated with lung cancer among Caucasians.

To derive a more precise estimation of the relationship between the excision repair cross-complementing rodent repair deficiency, group 2 (ERCC2) Lys751Gln polymorphism and lung cancer risk, a meta-analysis was performed. A total of 23 studies including 8137 cases and 9824 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with ERCC2 Gln allele when all studies were pooled into the meta-analysis (Lys/Gln versus Lys/Lys: odds ratio (OR)=1.10, 95% confidence interval (CI)=1.03-1.19; Gln/Gln versus Lys/Lys: OR=1.20, 95% CI=1.06-1.35; dominant model: OR=1.13, 95% CI=1.05-1.20; and recessive model: OR=1.15, 95% CI=1.03-1.29). In the subgroup analysis by ethnicity, significantly increased risk was only found for Caucasians (Gln/Gln versus Lys/Lys: OR=1.25, 95% CI=1.08-1.45; dominant model: OR=1.10, 95% CI=1.00-1.22; and recessive model: OR=1.22, 95% CI=1.06-1.40). When stratified by study design, statistically significantly elevated risks were found in hospital-based studies (Lys/Gln versus Lys/Lys: OR=1.12, 95% CI=1.03-1.22; Gln/Gln versus Lys/Lys: OR=1.24, 95% CI=1.06-1.44; dominant model: OR=1.15, 95% CI=1.06-1.24; and recessive model: OR=1.19, 95% CI=1.03-1.37) and population-based studies (Gln/Gln versus Lys/Lys: OR=1.57, 95% CI=1.12-2.20 and recessive model: OR=1.50, 95% CI=1.08-2.07). In the subgroup analysis whether or not the studies were matched on smoking, significantly increased risk was found not in those matched studies but in the unmatched studies (Lys/Gln versus Lys/Lys: OR=1.11, 95% CI=1.03-1.19; Gln/Gln versus Lys/Lys: OR=1.22, 95% CI=1.07-1.40; dominant model: OR=1.13, 95% CI=1.05-1.22; and recessive model: OR=1.18, 95% CI=1.04-1.33). In conclusion, this meta-analysis suggests that the ERCC2 Lys751Gln polymorphism may contribute to lung cancer susceptibility among Caucasians.

Prognostic and predictive value of clinical and biochemical factors in breast cancer patients with bone metastases receiving "metronomic" zoledronic acid

BackgroundTo assess prognostic and predictive effects of clinical and biochemical factors in our published randomized study of a weekly low dose (metronomic arm) versus a conventional dosage of zoledronic acid (conventional arm) in breast cancer patients with bone metastases.MethodsTreatment outcome of 60 patients with bone metastases were used to assess impacts of following potential prognostic factors, estrogen receptor status, lymph node status, 2 year-disease free interval (DFI), numbers of chemotherapy regimens administered, interventions, and serum levels of VEGF, N-telopeptide of type I collagen (NTx), CEA, and CA 15-3.ResultsIn univariate analyses, patients pretreated with 2 or fewer chemotherapy regimens, ER-positive tumors, 3 or fewer lymph nodes, DFI of more than 2 years, serum VEGF of less than 500 pg/mL after 3 months of intervention, serum CEA and CA 15-3 of less than ULN, and baseline serum NTx of less than 18 nM BCE had significantly longer progression free survival (PFS). The multivariate analysis showed that ER positivity (hazard ratio [HR], 0.295; 95% confidence interval [CI], 0.141-0.618; P = 0.001), serum VEGF of less than 500 pg/mL after 3 months of intervention (HR, 2.220; 95% CI, 1.136-4.338; P = 0.020), baseline serum NTx of less than 18 nM BCE (HR, 2.842; 95% CI, 1.458-5.539; P = 0.001), and 2 or fewer chemotherapy regimens received (HR, 7.803; 95% CI, 2.884-21.112; P = 0.000) were associated with a better PFS. When evaluating the predictive effect of the biochemical factors, an interaction between NTx and zoledronic acid intervention was shown (P = 0.005). The HR of weekly low dose versus a conventional dosage of zoledronic acid was estimated to be 2.309 (99% CI, 1.067-5.012) in patients with baseline serum NTx of more than 18 nM BCE, indicating a superiority of weekly low dose of zoledronic acid.ConclusionsER, serum VEGF level after intervention, and numbers of chemotherapy regimens administered are prognostic but not predictive factors in breast cancer patients with bone metastases. Patients with baseline serum NTx of more than 18 nM BCE might benefit more from weekly low-dose of zoledronic acid.Trial registrationClinicalTrials.gov unique identifier: ClinicalTrials.gov: NCT00524849

Cisplatin improves antitumor activity of weekly nab-paclitaxel in patients with metastatic breast cancer

Although nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is approved to be given every 3 weeks, weekly use of this drug is becoming a new standard of care in patients with metastatic breast cancer (MBC). This prospective Phase II study was conducted to improve the efficacy of weekly nab-paclitaxel with cisplatin in MBC patients. Seventy-three women with recurrent or MBC were eligible for participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m2 on day 1, day 8, and day 15, followed by cisplatin 75 mg/m2 on day 1, repeated every 28 days with a maximum of 6 cycles. The primary objective was investigator-assessed overall response rate (ORR). A high ORR of 67.1% was obtained, with rates of 80.6% for the first-line patients and 80% for patients not pretreated with taxanes. Among those who had objective responses, a large percentage of patients (83.7%) showed quickly remarkable tumor shrinkage during the first two cycles. The median progression-free and overall survival times were 9.8 and 26.9 months, respectively. For the patients receiving first-, second-, and third-line therapy or beyond, median progression-free survival was 11.7, 7.7, and 7.6 months, respectively (P=0.005). Molecular subtype was not significantly associated with ORR or disease progression. Grade 4 neutropenia occurred in 46 patients (63.0%), with febrile neutropenia found in 9 patients (12.3%). Grade 3 peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19 patients (26.0%). Efficacy of weekly nab-paclitaxel can be improved by adding cisplatin. The doublet is highly effective, with quick response, manageable toxicity, and possible equivalence across molecular subtypes in MBC patients.

The SUVmax for 18F-FDG correlates with molecular subtype and survival of previously untreated metastatic breast cancer

Aim The objectives of this study were to determine if the baseline SUVmax measured by 18F-FDG PET/CT correlates with molecular subtype and to explore the impact of baseline SUVmax on the survival of patients with metastatic breast cancer (MBC). Methods Patients with MBC were screened with PET/CT from February 2007 until December 2010. Multivariate linear regression analysis was performed to identify independent variable correlation with SUVmax. Prognostic variables identified by univariate analysis, with P < 0.1, were analyzed in the multivariate Cox model. Results A total of 244 MBC patients were eligible for this study. Multivariate linear regression analysis showed that molecular subtype, visceral metastasis, and number of metastatic organs could be used to predict the logarithmic values of SUVmax (lgSUVmax) for previous untreated MBC patients, whereas for those with 1 or more line previous treatment, the number of metastatic organs was identified as the only independent variable correlating with lgSUVmax. Cox regression analysis indicated that only in patients with previously untreated MBC did baseline SUVmax (continuous variable) act as an independent prognostic factor (hazard ratio = 1.049 for progression-free survival, 1.124 for overall survival). Conclusions Baseline SUVmax correlates with molecular subtypes only in previously untreated MBC patients. PET/CT imaging can be used as a potential prognostic tool for patients with newly diagnosed MBC.