PET Tracer Detects Estrogen Receptor Levels Across Breast Cancer Metastases, Study Finds

PET Tracer Detects Estrogen Receptor Levels Across Breast Cancer Metastases, Study Finds

A specific PET tracer is able to detect differences in estrogen receptor production throughout the body, and might help guide treatment of breast cancer patients whose cancer has spread, new study reveals.

The study, “18F-Fluoroestradiol Tumor Uptake Is Heterogeneous and Influenced by Site of Metastasis in Breast Cancer Patients,” conducted by researchers from the Netherlands, was published in The Journal of Nuclear Medicine.

Prognosis and treatment of metastatic breast cancer is largely influenced by the distribution and expression of estrogen receptor (ER). Although previous studies have already shown there is a high degree of heterogeneity on ER expression between the primary tumor and metastases, not much is known regarding estrogen receptor variability across different metastases and in the surrounding tissue.

Visualization and calculation of estrogen receptor levels in tumor lesions can be performed by positron emission tomography (PET) imaging using an imaging tracer called fluorine-18-fluoroestradiol (18F-FES) — a molecule that, once incorporated by the body, allows researchers to measure the amount of estrogen receptor present in the lesions.

This is an attractive imaging method that allows not only the visualization and quantification of ER levels in primary and secondary tumor sites, but also in normal tissue surrounding metastases.

In this study, researchers used 18F-FES PET to study ER heterogeneity in secondary metastases and normal surrounding tissue in a total of 91 patients diagnosed with ER-positive metastatic breast cancer, who performed scans between November 2009 until December 2014.

18F-FES was administered intravenously at a dose of approximately 200 MBq (megabecquerel, a measure of radioactivity) and the whole-body 18F-FES PET scan was performed 60 minutes after the tracer injection.

Tumor lesions with a diameter of 10 mm or more were considered ER-positive when they scored a maximum standardized uptake value (SUVmax) — a measure of the tracer’s uptake by the lesion that takes into account the amount of 18F-FES administered and the weight of the patient — equal or greater than 1.5.

“The results showed that approximately 50 percent of the patients had one or more estrogen-receptor negative lesions, while the primary tumor was estrogen-receptor positive,” Geke A.P. Hospers, an MD and PhD, and professor of medical oncology at the University of Groningen in the Netherlands, said in a press release. “This heterogeneity of ER expression is, therefore, really common, and it likely affects treatment outcome.”

A total of 1,617 secondary metastases in the bones (78%), lymph nodes (15%), lungs (4%), and liver (2%) were identified. Although the median tumor uptake varied substantially among patients, bone metastases registered higher values (2.61) in comparison with lymph nodes (2.29) and lung (2.23) metastases.

Tumor uptake also varied significantly in healthy tissues surrounding tumor lesions, with the highest values found in the bones.

Researchers then conducted a computer analysis that clustered patients based on their similarity, an approach that may help predict treatment responses in metastatic disease.

“By using cluster analysis on imaging characteristics and metastatic site, three distinct patterns of patients with ER-positive metastatic breast cancer were identified,” Hospers said.

The three clusters diverged mainly in the number of metastasis, metastasis site, and ER positivity.

The first included patients with a lower number of metastasis, which were rarely positive for the estrogen receptor. Patients in clusters 2 and 3, however, had several metastases positive for the receptor, but cluster 2 showed a median of 33 metastasis sites per patient, most in the bone.

Altogether, these findings indicate that 18F-FES uptake is highly heterogeneous between and within patients, as well as in tumor lesions and healthy surrounding tissues from different organs.

Now, researchers are convinced that distinguishing between these different patterns could be the key to develop personalized therapies suited for each patient.

“The knowledge of this heterogeneity by means of 18F-FES PET may support future specific treatment of metastasis,” Hospers said. “For example, one ER-negative lesion could be treated by radiotherapy, while the endocrine treatment is continued for the other ER-positive lesions.

“The three distinct patterns in ER-positive metastatic breast cancer that we identified with our analysis might be useful for future stratification in intervention studies and optimizing personalized treatment,” Hospers added.