Progress of Molecular Targeted Agents and its Role in Breast Cancer Management

ABSTRACT Human epidermal growth factor 2 (HER2) receptor and estrogen receptor have been regarded as the biologically relevant biomarker that plays an important role in the natural history of breast cancer. Increasing number of drugs targeting HER2 has been developed since introduction of trastuzumab and their role in the management of HER2-positive breast cancer are to be defined in on-going and future clinical trials. Combination of anti-HER2 molecular targeted treatments can produce pathological complete response in pre-operative setting, which envisions the cure of HER2-positive cancer without using cytotoxics. Moreover, some of molecular targeted drugs have shown promising results in overcoming endocrine resistance in hormone-receptor-positive disease. On the other hand, effective strategy for so-called ‘basal-like’ breast cancer, which has worse prognosis compared with other subtypes, is behind in its development. Various efforts have been put to narrowing down ‘basal-like’ to further subtypes, to identify clinically relevant biomarkers and to develop effective molecular targeted treatments for this subtype. Introduction of expensive molecular targeted drugs have raised contemporary issues: valid end points for registration and other clinical trials need of more accurate predictive markers, quality control of biomarkers, etc. Because of limited resources, there is a need for innovative clinical trial design that enables simultaneous investigation of efficacy and rational biomarkers for newly developed molecular targeted agents. The development of appraisal system for molecular targeted drugs involving multiple stake-holders is warranted in drug-approval process and also in individual decision-making in a clinical setting.