Conclusions And Possible Future Perspectives

Early detection of cancer must ultimately move towards population screening for asymptomatic cases. A blood-based assay is clearly an attractive idea for the future, which should be acceptable to the general population. Such an assay might focus on the detection of a combination of factors, identifiable in both circulating tumor cells and circulating nucleic acids. However, before a multibio-marker test can be developed and validated, a number of key issues remain to be resolved. Although the majority of plasma/serum DNA alterations concur with those seen in tumor

DNA, several studies have shown alterations in plasma or tumor only (e.g. Silva et al37 and Shaw et al50). Garcia et al74 showed that heterogeneous tumor clones, and not PCR artefacts, could explain some nonmatched alterations between plasma and tumor DNA. Clearly, molecular markers which show homogeneous alterations in tumor are desired for analysis in plasma DNA. DNA methylation-based biomarkers, and detection of common mutations, are probably the most attractive for development, although each will require close scrutiny of assay sensitivity and specificity. DNA changes have the advantage of being qualitative (present or absent) rather than quantitative, such as for mRNA and pro-tein.50 However, given the differences in amounts of free DNA detected between cancers and controls, it might be useful to combine both qualitative and quantitative criteria for detection of tumor-specific DNA in blood. A number of research groups, including our own, are currently following up different cohorts of patients with a range of molecular markers and assays. However, additional studies will be needed in order to validate the most useful markers for plasma/serum DNA and/or RNA analysis in large cohorts of breast cancer patients and other tumor types. Ultimately, the development of a high-throughput sensitive blood-based test may well be achievable for early detection of breast cancer.

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