Heterogeneity of breast cancer among patients and implications for patient selection for adjuvant chemotherapy

Although the benefits of adjuvant chemotherapy are not controversial, the absolute effect of such therapy is small. Therefore, there is a need to identify biomarkers that can help select patients with localized breast cancer for treatment. Despite intense research in this field, no biomarker has been shown to be useful to predict benefit of adjuvant chemotherapy in daily practice. This can partially be explained by the fact that breast cancer is composed of several distinct subclasses, as shown by large-scale genomic analyses. In this review, we discuss why the current research approach based on a single biomarker is limited by the heterogeneity of cancer among patients. We then propose three solutions to improve the research strategies in this field: investigate one biomarker in a single homogeneous subclass to improve its predictive value; study the predictive value of multibiomarker assays in larger populations; and use functional pathways to predict the efficacy of a given drug.