FES PET Predicts Response to Endocrine Treatment

Fran Lowry

June 18, 2012

June 18, 2012 (Miami Beach, Florida) — In patients with newly diagnosed metastatic breast cancer, 18F-fluoroestradiol (FES) positron emission tomography (PET) imaging is a noninvasive measure of breast cancer estrogen-receptor (ER) expression. The results correlate well with standard biopsy and immunohistochemistry measurements and can predict the response of the tumor to endocrine therapy.

These findings, which represent the early results of a phase 2 study, were presented here at the SNM 2012 Annual Meeting.

"FES is not taken up in tumors that are ER-negative; therefore, patients with breast cancer that is ER-negative have disease that is unlikely to respond to endocrine therapy," lead author Lanell M. Peterson, PhD, from the University of Washington Medical Center in Seattle, told Medscape Medical News.

Dr. Lanell Peterson

"FES imaging in patients with metastatic breast cancer can also detect and measure ER expression in areas of disease that are difficult to biopsy, such as bone metastases," she said.

"This study shows that FES PET works well in patients with newly diagnosed metastatic breast cancer and that the method is ready for more widespread clinical testing," Dr. Peterson added.

She and her colleagues previously showed that FES uptake predicts response to salvage endocrine therapy. The current study, a National Cancer Institute-sponsored Investigational New Drug enabling study, extends that work to look at response to therapy in patients with newly diagnosed metastatic breast cancer undergoing first-line endocrine therapy.

"FES is an estrogen labeled with F-18, a positron emitter, so that it can be imaged by PET," Dr. Peterson explained.

"FES is taken up in tumors that are ER-positive.... ER-positive tumors have been shown to be responsive to endocrine therapy, whereas ER-negative disease requires chemotherapy treatment. FES can detect tumors that are unlikely to respond to endocrine therapy without the need to biopsy each metastatic lesion, so patients can avoid therapy that is unlikely to help them," she explained.

The study involved 19 patients with de novo (n = 4) or newly diagnosed metastatic breast cancer (n = 15). All patients had documented ER-positive primary disease and previously untreated metastatic breast cancer.

The researchers compared lesions that were clinically defined with an FDG PET scan and FES PET images. "This allowed us to locate tumors considered to be FES-negative," Dr. Peterson said.

The researchers also measured the amount of FES that was taken up at a few key "index" sites of disease. "The study was purely observational; imaging results were not used to direct clinical therapy," she said.

The patients were given standard endocrine therapy. Disease was monitored for up to 6 months to determine clinical response.

The study found that 7 of the patients (37%) had at least 1 site of qualitatively absent FES uptake. Of these, 4 were evaluated for response and 3 (75%) were found to have progressive disease.

A metastatic lesion was biopsied in 15 of the patients. The researchers found that ER expression in the metastatic lesion biopsy was absent in 3 of the patients (20%); all 3 had low FES uptake.

Additionally, stable disease was noted in 5 of 15 patients (33%), whereas 4 (27%) had a partial response and 6 (40%) had progressive disease.

Of the 9 patients with stable disease or a partial response, only 1 (11%) had a qualitatively FES-negative site of disease.

"The biopsy data correlated well with FES imaging, with perfect agreement between ER biopsy and low FES uptake," Dr. Peterson said. "Metastatic breast cancer that includes sites of disease that are ER-negative does not respond to first-line endocrine therapy."

These early results suggest that FES PET can measure ER expression in newly diagnosed metastatic breast cancer and that the absence of FES uptake is predictive of a lack of response to endocrine therapy. They are similar to previous FES results in patients receiving salvage endocrine therapy, she concluded.

"Cooperative groups are now working on a protocol that will include FES PET imaging. The agent is investigational, so not yet available for clinical care, but doctors should encourage their patients to take part in clinical trials if they have access to a study," she added.

Dr. Otto Boerman

Commenting on this study for Medscape Medical News, Otto C. Boerman, PhD, professor of radiochemistry at Radboud University Nijmegen Medical Center in the Netherlands, said that FES PET could play a role in helping clinicians make an earlier switch to nonhormonal therapies in patients who are not responding to endocrine therapy.

"The idea here is that as soon as the tumor loses its ER expression, it can no longer be treated with hormone therapy," said Dr. Boerman, who moderated the session.

"As soon as you see that a metastatic lesion or a primary lesion has become FES-negative, you can switch to a second-line therapy. But you need a very high negative predictive value. You really have to rely on the FES scan, which is the tricky thing," he said.

Dr. Peterson and Dr. Boerman have disclosed no relevant financial relationships.

SNM 2012 Annual Meeting: Abstract 329. Presented June 12, 2012.


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