Accurate staging plays a crucial role in the management of breast cancer, as it determines treatment plans and informs prognosis. Conventional staging methods primarily utilise 18F-FDG PET, which detects metabolic activity by measuring glucose uptake in cancerous tissues. However, this approach has limitations when applied to low-grade oestrogen receptor (ER)-positive breast cancers, as these tumours typically exhibit lower glucose metabolism, resulting in reduced 18F-FDG uptake. Consequently, staging errors may occur, affecting treatment strategies and patient outcomes.
An alternative imaging approach, 18F-FES PET, targets ER expression rather than glucose metabolism. As ER-positive breast cancers express oestrogen receptors, this tracer may provide a more accurate visualisation of tumour spread in these cases. A recent study published in Radiology examines the diagnostic performance of both PET tracers in staging patients with grade 1 and 2 ER-positive breast cancer, assessing their accuracy in identifying primary tumours, regional lymph node involvement and distant metastases.
Diagnostic Performance of 18F-FDG and 18F-FES PET
Both 18F-FDG PET and 18F-FES PET demonstrated high sensitivity and specificity in detecting metastatic disease. However, differences were observed in overall staging accuracy. The study found that 18F-FES PET correctly staged 83% of cases, whereas 18F-FDG PET correctly staged 71%. These results suggest that 18F-FES PET may provide superior staging accuracy in low-grade ER-positive breast cancer, particularly in cases where 18F-FDG PET performance is suboptimal.
Histological subtype and tumour grade influenced the accuracy of both imaging modalities. In cases of lobular carcinoma, 18F-FES PET achieved a correct staging rate of 90%, compared with 70% for 18F-FDG PET. Similarly, in grade 1 tumours, 18F-FES PET correctly staged 92% of cases, whereas 18F-FDG PET correctly staged only 58%. These findings highlight the potential advantage of 18F-FES PET in detecting low-grade ER-positive breast cancers, where 18F-FDG PET may fail to provide reliable results.
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Another key difference between the two modalities was their performance in staging regional lymph nodes. The study found that 18F-FDG PET incorrectly staged lymph nodes in 14% of cases, while 18F-FES PET correctly staged all cases. This suggests that 18F-FES PET provides a more precise evaluation of nodal involvement, reducing the risk of understaging or overstaging disease. Accurate lymph node assessment is critical in determining the appropriate course of treatment, as nodal involvement influences decisions regarding surgery, radiotherapy and systemic therapy.
Impact on Disease Management
The findings indicate that 18F-FES PET has the potential to refine staging and, in turn, influence treatment strategies for patients with low-grade ER-positive breast cancer. In several cases, it identified additional malignant lesions that were not detected by 18F-FDG PET. This is particularly relevant in patients where staging results could impact clinical decision-making, such as those being considered for curative-intent treatment or local ablative therapy for oligometastatic disease.
Moreover, 18F-FES PET provided improved visualisation of tumour spread in some cases, leading to adjustments in disease management. The ability to accurately determine the extent of disease may prevent unnecessary interventions or guide more targeted treatments. This suggests that 18F-FES PET could serve as a complementary or alternative imaging tool for cases in which 18F-FDG PET provides inconclusive or incomplete staging results.
Despite these advantages, it is important to consider that 18F-FES PET is not without limitations. One of its primary drawbacks is its inability to reliably detect liver metastases due to high physiological uptake in the liver. Additionally, false-positive findings were reported in some cases, particularly in cervical and mediastinal lymph nodes. These findings, which were ultimately classified as benign based on fine-needle aspiration, highlight the potential for false-positive results that may necessitate further histopathological verification.
Considerations and Future Research
While the results suggest that 18F-FES PET may offer improved staging accuracy compared with 18F-FDG PET, further research is needed to establish its role in clinical practice. Larger-scale studies could provide more definitive evidence on whether 18F-FES PET should replace or supplement 18F-FDG PET in staging low-grade ER-positive breast cancer. Additionally, further investigation is required to refine patient selection criteria, ensuring that 18F-FES PET is used in cases where it offers the greatest benefit.
Another avenue for future research is the development of optimised diagnostic pathways incorporating both imaging modalities. One potential approach is a sequential diagnostic strategy, in which patients undergo one PET scan initially and proceed to a second scan only if the first is inconclusive. Such a strategy could enhance staging accuracy while minimising unnecessary imaging procedures and associated costs.
The study findings also raise questions about the potential broader clinical applications of 18F-FES PET. While its primary use has been in staging breast cancer, its ability to visualise ER-positive lesions could extend to other ER-expressing malignancies. Additional research could explore its utility in conditions such as metastatic breast cancer, where monitoring ER expression over time may provide valuable insights into tumour response to therapy.
The findings of this study suggest that 18F-FES PET offers a viable alternative to 18F-FDG PET in staging grade 1 and 2 ER-positive breast cancer, particularly in cases where conventional imaging is inadequate. It demonstrated higher staging accuracy in low-grade and lobular tumours and provided superior assessment of regional lymph node involvement. This improved diagnostic precision may have significant implications for treatment planning, potentially leading to better-targeted therapies and improved patient outcomes.
However, despite these promising results, further research is required to validate the role of 18F-FES PET in routine clinical practice. Large-scale studies should determine whether its use should be integrated into standard staging protocols, either as a primary imaging tool or as a supplementary option when 18F-FDG PET results are inconclusive. Given the potential impact on disease management, ongoing investigation into the optimal application of 18F-FES PET is warranted to ensure that patients with low-grade ER-positive breast cancer receive the most accurate and effective staging possible.
Source: Radiology
Image Credit: iStock
