Biomarker discordance during tumor progression.

Molecular biomarkers are used by clinicians to guide selection of the most appropriate systemic therapy for metastatic breast cancer: endocrine therapy, chemotherapy, or human epidermal growth factor receptor 2 (HER2) – targeted therapy, such as trastuzumab or lapatinib. With increased understanding that molecular biomarker status can change during tumor progression such that biomarker status is discordant between the primary tumor and metastatic tumors, interest in the role of biopsy of metastatic disease has increased. However, biopsies of suspected metastases are not always performed in routine oncologic practice. Furthermore, whether selecting targeted therapy on the basis of the estrogen receptor (ER), progesterone receptor (PR), or HER2 status of metastatic tumors can prolong survival is not known, and selection of targeted therapy on the basis of the molecular biomarker status of metastatic disease is controversial. Research has shown that patients with discordance in molecular biomarker status between the primary tumor and metastatic tumors have poor survival rates. However, it is unclear whether these differences in biomarker status are a result of preanalytic variables or reflect true differences in biology based on heterogeneity of clonal populations in breast cancer.