ABSTRACT
As indicated by many researchers (e.g., Simon and Maitournam, 2004; Maitournam and Simon, 2005; Casciano and Woodcock, 2006; Dalton and Friend, 2006; Varmus, 2006), the disease targets at the molecular level can be identiŒed after completion of the Human Genome Project (HGP). As a result, the importance of diagnostic tests for the identiŒcation of molecular targets increases as more targeted clinical trials will be conducted for the individualized treatment of patients (personalized medicine). For example, based on the risk of distant recurrence determined by a 21-gene Oncotype DX® breast cancer assay, patients with a recurrence score of 11-25 in the TAILORx (Trial Assigning Individualized Options for Treatment) trial sponsored by the United States National Cancer Institute (NCI) are randomly assigned to receive either adjuvant chemotherapy and hormonal therapy or adjuvant hormonal therapy alone (Sprarano et al., 2006). On the other hand, based on a 70-gene molecular signature, the MINDACT (Microarray in Node-negative Disease may Avoid ChemoTherapy) trial randomizes patients with a low-risk molecular prognosis and a high-risk clinical prognosis to the use of clinicopathologic criteria or gene signature in treatment decisions for the possible avoidance of chemotherapy (MINDACT, 2006). These two trials have an important implication for future individualized treatments for thousands of breast cancer patients (Swain, 2006). The Oncotype DX used in the TAILORx trial is a reverse transcriptase-polymerase chain reaction (RT-PCR) assay based on 21 genes, while the MINDACT trial employs a 70-gene molecular signature derived from the microarray (Van de Vijver et al., 2002; van’t Veer, 2002; Paik et al., 2004, 2006).
