Prognostic signatures of breast cancer: Perou's molecular subtypes and Schmidt's metagenes

The search for biomarkers predicting metastasis-free survival or overall survival identified two key factors, namely estrogen receptor expression (Osborne et al., 1980) and the degree of proliferation (Gentili et al., 1981). However, a coherent picture did not emerge until the advent of gene array technology (Sorlie et al., 2001; Perou et al., 2000; Rouzier et al., 2005; review: Schmidt et al., 2009a). Several groups have identified sets of genes that are associated with increased risk of metastasis (van’t Veer et al., 2002; Wang et al., 2005; van de Vijver et al., 2002; Foekens et al., 2006). It has become clear that these genes mostly represent proliferation, estrogen receptor alpha (ESR1) and immune cell associated genes (Paik et al., 2004; Sotiriou et al., 2006; Oh et al., 2006; Fan et al., 2006; Desmedt et al., 2007; Schmidt et al., 2008). Two basic discoveries have particularly contributed to the current knowledge on how gene expression relates to prognosis: