A 48-year-old woman with a history of estrogen receptor-positive (ER+), HER2-negative breast cancer treated with surgery, chemotherapy, radiotherapy, and endocrine therapy (Tamoxifen) presented with sternal pain four years after initial diagnosis. 18F-FDG PET/CT (A) demonstrated a hypermetabolic sternal lesion suspicious for metastatic disease. A corresponding osteolytic lesion of the sternum was identified on CT imaging. In contrast, 18F-FES PET/CT (B) was performed after a 6-week discontinuation of tamoxifen, with no other endocrine therapy administered during the washout period, and showed no tracer uptake in the same lesion. Subsequent biopsy confirmed metastatic breast carcinoma with preserved ER expression (C). Histopathology revealed tumor infiltration on hematoxylin–eosin staining and strong ER positivity on immunohistochemistry. This discordance illustrates a key limitation of 18F-FES imaging: tracer uptake reflects functional receptor availability rather than receptor expression [1, 2]. Potential explanations for the absence of FES uptake despite preserved ER expression include persistent receptor occupancy, altered receptor functionality, tumor heterogeneity, impaired ligand-binding capacity, or other biological factors affecting tracer binding. However, the precise mechanism underlying this discordance cannot be determined from this single case [3].
The case highlights a potential pitfall in interpreting FES PET, particularly in previously treated patients. A negative FES scan should not be interpreted as absence of ER expression, especially when clinical or metabolic findings are suspicious. Recognition of this limitation is essential to avoid misclassification of ER status and inappropriate therapeutic decisions. Multimodal correlation, including FDG PET and histopathology, remains critical in such discordant cases (Fig. 1).
Fig. 1.
Multimodal imaging and histopathological correlation of sternal metastasis. (A) 18F-FDG PET/CT demonstrating intense hypermetabolic activity in the sternal lesion, consistent with metabolically active metastasis. (B) 18F-FES PET/CT performed approximatively 2 months later, following a 6-week discontinuation of endocrine therapy, showing no significant tracer uptake in the sternal lesion. (C) Immunohistochemistry of the sternal biopsy demonstrating positive estrogen receptor (ER) expression in tumor cells
Author contributions
All authors contributed to the study conception and design. The first draft of the manuscript was written by Maria-Joao santiago-Ribeiro, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
No funding was received for this study.
Declarations
Ethics approval and consent to participate
This study was performed in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the patient.
Competing interests
The authors declare no competing interests.
Footnotes
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References
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