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Classification of NSCLC Patients for EGFR Inhibitor BenefitsOnly a subset of patients with non–small-cell lung cancer (NSCLC) respond to gefitinib and erlotinib, small-molecule tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR), but a larger fraction appear to have prolonged stabilization of disease. Taguchi et al. (p. 838) investigated whether mass spectrometic features in pretreatment blood serum might be used to classify NSCLC patients according to their outcomes after treatment with these drugs. To do so, they developed a matrix-assisted laser desorption/ionization (MALDI) algorithm from a training set of patients with known outcomes. They tested the algorithm on two independent validation cohorts. In both cohorts, patients classified in the "good" groups before treatment survived for statistically significantly longer after treatment with EGFR inhibitors than patients classified in the "poor" groups. Outcomes of patients in control cohorts that did not receive EGFR inhibitor treatment were not classified correctly by the algorithm, indicating that it was not merely classifying patients according to prognosis but was specific for benefit from EGFR inhibitors. The authors note that the results still need to be confirmed in additional patient cohorts before the algorithm could be used to select NSCLC patients for EGFR inhibitor treatment.
In an editorial, Tsao et al. (p. 826) note that previous attempts to use serum mass spectrometric proteomics have suffered from problems with reproducibility of the data, and they applaud the authors for having used normalization and preprocessing techniques that reduced the differences among proteomic profiles generated at two different institutions. An important next step will be to identify the proteins that comprise the signature.
Comparing Cisplatin, Carboplatin for Treatment of Advanced NSCLC
Both cisplatin and carboplatin have been shown to be effective in treating patients with advanced NSCLC. Carboplatin is associated with fewer side effects than cisplatin, but whether these agents have the same clinical efficacy was not known. Ardizzoni et al. (p. 847) analyzed the results of nine trials that compared the efficacy of these drugs in treating patients with advanced NSCLC and found that response rates were higher among those treated with cisplatin. Furthermore, cisplatin treatment was associated with longer survival than carboplatin among patients with nonsquamous tumors who were also treated with third-generation drugs such as gemcitabine, taxanes, and vinorelbine.
In an editorial, Pfister and Azzoli (p. 828) outline additional evidence supporting the use of cisplatin over carboplatin in NSCLC patients who may be cured. They caution against the overzealous use of cisplatin in patients with metastatic NSCLC and serious comorbidities.
Proteomic Signature and Outcome in Patients with NSCLC
NSCLC patients with a poor prognosis cannot be accurately distinguished from those with good prognosis. Yanagisawa et al. (p. 858) used mass spectrometry of tumor and normal lung tissue to derive a 25-signal proteomic signature that was associated with both relapse-free and overall survival in NSCLC patients. This signature appears to distinguish NSCLC patients with good prognosis from those with poor prognosis. Proteins corresponding to a portion of the signals were also identified. The authors conclude that determining the biologic functions of the proteins in the signature may help to identify targets for the development of improved NSCLC treatments.
Integrin 
7 Mutations and Various Types of Human Cancers
Integrins are major cellular adhesion molecules, but their involvement in carcinogenesis is not well defined. Ren et al. (p. 868) investigated whether integrin 7 has a role in carcinogenesis. Integrin 7 was mutated in various tumor types, it had tumor suppressor and cell migration inhibitory activities, and its expression level was associated with survival of cancer patients and mice bearing xenograft tumors. The authors conclude that integrin 7 appears to be a tumor suppressor that operates by suppressing tumor growth and retarding cell migration.
Aspirin, Nonaspirin NSAIDs, and Cancer Incidence and Mortality
The potential chemopreventive effects of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) are unclear and may be altered by smoking. To investigate associations between the use of aspirin and nonaspirin NSAIDs and cancer incidence and mortality, Bardia et al. (p. 881) assessed survey data on aspirin and nonaspirin NSAID use and smoking history from the Iowa Women's Health Study and cancer incidence and death from the Iowa Surveillance, Epidemiology, and End Results Cancer Registry and death certificates. During the average 10-year follow-up of approximately 22,500 postmenopausal women, 3,487 were diagnosed with cancer and 1,193 died from cancer. Aspirin use was associated with decreased cancer incidence (age-adjusted rates of 147 and 170 per 10,000 person-years for ever and never smokers, respectively) and mortality (47 and 52 per 10,000 person-years). The inverse association with aspirin was stronger, although not statistically significantly so, among former and never smokers than current smokers. No associations were observed with nonaspirin NSAIDs. The authors conclude that the use of aspirin—but not NSAIDs—was associated with decreased cancer incidence and mortality, and the relationship was more pronounced among former and never smokers than current smokers.
Inflammation, C-Reactive Protein, and Breast Cancer Risk
Inflammation may contribute to breast cancer tumorigenesis, but little research has been done on this hypothesis. Zhang et al. (p. 890) analyzed data from nearly 28,000 apparently healthy women aged 45 years and older who had a measurement of their plasma C-reactive protein (CRP) level, a marker of systemic inflammation. The women were followed for an average of 10 years as part of the Women's Health Study. During the follow-up period, 892 women were diagnosed with invasive breast cancer. Baseline plasma CRP level was not associated with breast cancer risk. The authors conclude that baseline plasma CRP levels are not associated with an increased risk of breast cancer in apparently healthy women.
Incidence of Intra- and Extrahepatic Cholangiocarcinoma in Denmark
In several countries, including the United States, incidence rates of intrahepatic cholangiocarcinoma are increasing while those of extrahepatic cholangiocarcinoma are decreasing. Jepsen et al. (p. 895) examined whether such opposing trends could be confirmed in Denmark. In an analysis of Danish data from 1978 through 2002, they found that incidence rates of these cancers were nearly identical throughout the study period and that the incidence of both cancers decreased over time. The authors conclude that the Danish data did not confirm the findings in the United States and several other countries.
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J Natl Cancer Inst 2007 99: 847-857.
J Natl Cancer Inst 2007 99: 858-867.
7 Mutations in Prostate Cancer, Liver Cancer, Glioblastoma Multiforme, and Leiomyosarcoma
J Natl Cancer Inst 2007 99: 868-880.
J Natl Cancer Inst 2007 99: 881-889.
J Natl Cancer Inst 2007 99: 890-894.
J Natl Cancer Inst 2007 99: 895-897.
J Natl Cancer Inst 2007 99: 1054.
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