Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis

Objective: A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase(PI3K) and mitogen-activated protein kinase(MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) treatment of non-small cell lung cancer(NSCLC) patients.Methods: Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3 CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios(ORs) for objective response rate(ORR) and hazard ratios(HRs) for progression-free survival(PFS) and overall survival(OS) were calculated.Results: Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval(CI), 0.13-0.35], shorter PFS(HR =1.56; 95% CI, 1.27-1.92), and shorter OS(HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3 CA significantly predicted shorter OS(HR =1.83; 95% CI, 1.05-3.20), showed poor ORR(OR =0.70; 95% CI, 0.22-2.18), and shorter PFS(HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs.Conclusion: K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFRTKIs. PIK3 CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3 CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery？

Objective: Survival and treatment of patients with microinvasive breast cancer(MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy.Methods: In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer(AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups.We compared the 5-year disease-free survival(DFS) and overall survival(OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months(13-104months).Results: The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the nonchemotherapy group were 89.7% and 100%. Results indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS(P=0.223) or OS(P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2% vs. 86.5% between low Ki-67(≤20%) and high Ki-67(>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval(CI), 1.969-139.724; P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149(95% CI, 3.702-99.057; P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients(P=0.014), but not those who overexpress Ki-67(P=0.105).Conclusions: Patients with MIBC who overexpress Ki-67 and with negative hormonal receptors have relatively substantial risk of relapse within the first five years after surgery. However, adjuvant chemotherapy can only improve the outcomes of ER(-)/PR(-)patients, but not those who overexpress Ki-67. Further studies with prolonged follow-up of large cohorts are recommended to assess the prognostic significance and treatment of this lesion.