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Multicenter Study
. 2012 Aug 16;14(4):R119.
doi: 10.1186/bcr3244.

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

Renata Duchnowska, Rafał Dziadziuszko, Tomasz Trojanowski, Tomasz Mandat, Waldemar Och, Bogumiła Czartoryska-Arłukowicz, Barbara Radecka, Wojciech Olszewski, Franciszek Szubstarski, Wojciech Kozłowski, Bożena Jarosz, Wojciech Rogowski, Anna Kowalczyk, Janusz Limon, Wojciech Biernat, Jacek Jassem; Polish Brain Metastasis Consortium
Multicenter Study

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

Renata Duchnowska et al. Breast Cancer Res. .

Abstract

Introduction: We investigated the status of estrogen receptor alpha (ERα), 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. ERα, 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 ERα 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 ERα (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.

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Figures

Figure 1
Figure 1
Phenotypes for ER (A), PR (B), and HER2 (C) in primary tumors and their matched brain metastases. ER, estrogen receptor; PR, progesterone receptor; HER2, epidermal growth factor receptor 2.
Figure 2
Figure 2
Overall survival in relation to ERα conversions. Log-rank P = 0.041 (all comparisons); P = 0.005 (ER-/ER- versus others); HR = 1.84 (1.20 to 2.83; ER-/ER- versus others).
Figure 3
Figure 3
Overall survival in relation to progesterone receptor (PR) conversions. Log-rank P = 0.037 (all comparisons); P = 0.005 (PR-/PR- versus others); HR = 1.89 (1.22 to 2.94; PR-/PR- versus others).
Figure 4
Figure 4
Overall survival in relation to epidermal growth factor receptor 2 (HER2) conversions. Log-rank P = 0.944 (all comparisons); P = 0.582 (PR-/PR- versus others); HR = 1.13 (0.73 to 1.74; HER2-/HER2- versus others).
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