Receptor Conversion in Breast Cancer Metastases.

Abstract Background: Since breast cancer metastases are not usually biopsied due to their often inaccessible locations, choice of systemic treatment for metastatic breast cancer is usually based on tissue characteristics of the primary tumor, as determined by immunohistochemistry. However, pilot studies have shown that the immunophenotype of breast cancer metastases may be different from that of the primary tumor (“receptor conversion”). This means that many metastatic patients may not get the appropriate systemic treatment. The pilot studies published so far are however small and methodologically suboptimal as original staining data of the primary tumors were often used, and decalcified bone metastases were included that may give rise to false negative immunohistochemistry. Therefore, definite conclusions that may chance clinical practice could not be drawn. The aim of this study was therefore to study receptor conversion for ERα, PR, and HER2 in a large group of (non-bone) breast cancer metastases, restaining all primary tumors and metastases with current optimal immuno-histochemical methods.Methods: A group of 150 distant breast cancer metastases from different distant sites (79 skin, 33 liver, 22 lung, and 16 brain) was immunohistochemically stained for ERα, PR, and HER2, and receptor expression was compared to that of the primary tumor.Results: Receptor conversion for ERα, PR and HER2 occurred in 6%, 27.4% and 2.7% of the 150 patients, respectively. Conversion was mainly from positive to negative for ER and PR, and from negative to positive for HER2. Receptor conversion seemed to occur especially in liver metastases (ER 9.1%, PR 36.4%, HER2 6.1%) while brain metastases showed no conversion for ER and HER2.Conclusion: Receptor conversion in breast cancer metastases indeed occurs, is rare for ER and HER2, but is more frequent for PR, and may be most outspoken in liver metastases. This underlines the importance of having breast cancer metastases frequently biopsied when possible. Alternatively, molecular imaging strategies are warranted for sites that are difficult to biopsy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4145.