Molecular profiling has changed the treatment landscape in advanced non-small-cell lung cancer. Accurately identifying the tumours that harbour sensitizing EGFR mutations, the most common targetable molecular alteration, as well as those with acquired resistance mutations (e.g. T790M) on treatment is a high clinical priority. The current clinical gold standard is genotyping of tumour specimens. However, the practical utility of this approach is limited by the lack of available tissue and the potential complications associated with biopsies. With the advent of newer sequencing assays, it has become feasible to assess tumour genomics via a blood sample, termed a 'liquid biopsy'. In this review, we summarize the available techniques for liquid biopsies and their applicability for detecting sensitizing and resistance EGFR mutations and how these results may be used for making treatment decisions.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

Background Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk. Methods We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of four population-based endometrial cancer case-control studies of women 45–74 years of age (1,712 cases and 2,134 controls) during 1985–2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews. Results Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14–0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree. Conclusions In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.

No abstract

No abstract