Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain

Introduction: We investigated the status of estrogen receptor alpha (ER alpha), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival. Methods: The study group included 120 breast cancer patients. ER alpha, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization. Results: Using the Allred score of >= 3 as a threshold, conversion of ER alpha and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ER alpha (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival. Conclusions: Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.