Effect of KRAS mutational status in advanced colorectal cancer on the outcomes of anti-epidermal growth factor receptor monoclonal antibody therapy: a systematic review and meta-analysis.

BACKGROUND: Emerging data suggest that somatic KRAS mutation in advanced colorectal cancer is a strong predictor of non-response to anti-epidermal growth factor receptor antibody (anti-EGFR) therapy. PATIENTS AND METHODS: A comprehensive search through March 2010 identified randomized controlled trials in metastatic colorectal cancer that evaluated chemotherapy regimens or best supportive care, with and without anti-EGFR therapy. Outcomes included progression-free survival (PFS), median overall survival (OS), and predictive test performance. RESULTS: In pooled data from 8 trials with 5325 patients, the addition of anti-EGFR to standard chemotherapy resulted in improved PFS (HR 0.66 [95% CI, 0.53-0.82]) in patients with wild-type KRAS in the tumor tissue, but not in patients with KRAS mutation (HR 1.07 [95% CI, 0.91-1.27]). Anti-EGFR treatment in the wild-type group did not significantly improve median OS. As a predictive biomarker, KRAS mutation had a positive likelihood ratio of 2.0 (95% CI, 1.45-2.76) in predicting nonresponse to anti-EGFR treatment. CONCLUSION: In patients with advanced colorectal cancer, the addition of anti-EGFR treatment to standard chemotherapy improves PFS for those with wild-type, but not mutant KRAS status. KRAS gene mutation testing provides a fair biomarker in predicting non-response to anti-EGFR treatment.

Impact of initial surgical margins and residual cancer upon re-excision on outcome of patients with localized breast cancer.

BACKGROUND: A significant proportion of patients undergoing breast conservation therapy require additional operations to obtain clear margins. The aim of this study was to assess the impact of initial margins and residual carcinoma found on second surgery on the outcomes of breast cancer patients. METHODS: In this retrospective study, Cox proportional-hazard regression analysis was performed to evaluate data from 437 patients with stage I to IIIA breast cancer who underwent initial breast-conserving surgery between 1994 and 2004. RESULTS: The distant recurrence rate was higher among patients with initial positive margins than among those with initial negative margins (15.5% vs 4.9%; hazard ratio, 3.6; 95% confidence interval 1.5-8.7; P = .003). For patients who had underwent second surgery, the finding of a residual invasive carcinoma was associated with increased risk for distant recurrence (22.8% vs 6.6%; hazard ratio, 3.5; 95% confidence interval, 1.8-7.4; P = .0001). CONCLUSION: Invasive residual carcinoma found during subsequent surgery after initial compromised margins is an important prognostic marker for distant recurrence.