Is There a Role for FES-PET Imaging in Assessing ER Status and Extent?

Gary Ulaner, MD, PhD: A second potential application for an FES-PET [F-18 fluoroestradiol-positron emission tomography] scan is the ability to assess estrogen receptor [ER] status in lesions that you may find difficult or impossible to biopsy. The best example of this possibly is brain metastases. This was published from the University of Washington in Seattle. This is a patient with an estrogen receptor-positive breast cancer who unfortunately developed a lesion in the brain on MR [magnetic resonance] as shown in the image on the left. If you want to see if this is a lesion that’s being caused by metastasis from the ER+ breast cancer, one way to do that is to do a biopsy. But obviously, that’s quite invasive, putting a needle into the skull into the brain parenchyma in order to sample this deep lesion. Instead of doing that, an FES-PET scan can be performed, which demonstrates indeed this lesion is avid for the ER-targeting FES-PET agent, confirming with very high confidence that this is a metastasis from the estrogen receptor-positive breast cancer that the patient unfortunately suffers from.

A third potential application for FES-PET CT is helping to solve clinical dilemmas, inconclusive results on other imaging modalities. This is a manuscript out of a group from the Netherlands in which they followed a hundred patients that had inconclusive imaging on what we consider standard of care bone scans or CT scans. For example, this patient had some slight uptake on their bone scan in the spine. It was unclear whether this represented metastases or whether these were benign degenerative changes. The FES-PET scan that was subsequently performed in this patient could demonstrate multiple sites of disease within bones, providing strong confidence that this was representative of disease rather than benign degenerative changes, and greatly influencing the patient’s future course of treatment. For over 85% of patients who had inconclusive imaging results on CT or bone scan, the FES PET could more accurately define the extent of malignancy in these patients.

Finally, the FES-PET scan is being looked at for the evaluation of extent of disease. Now, extent of disease has predominantly been the role of FDG [fluorodeoxyglucose]-PET, as we’ve shown previously. But certain breast cancers are not particularly metabolically active. They don’t pick up a lot of FDG. Many of those tumors happen to be very strongly estrogen receptor-positive. Thus, using an agent that can detect the estrogen receptor may be more valuable for evaluating extent of disease than the metabolic tracer FDG-PET.

At the Hoag Family Cancer Institute, we have a prospective clinical trial evaluating FES-PET versus standard of care FDG-PET or CT bone scan to evaluate whether the FES-PET can provide value in assessing extent of disease, in 2 groups of patients. The first patients were newly diagnosed with locally advanced disease, so there is enough disease that there is a risk for distant metastasis but not proven to be distant metastasis. In these patients, the patients received both standard of care imaging as well as the FES-PET CT. And then, lesions that are suspicious undergo biopsy for pathological confirmation. As we have seen in several patients, whereas standard of care imaging like CT bone scan might fail to detect distant metastasis, in this patient with presumed locally advanced disease, the FES-PET identified bone metastases in multiple sites, which demonstrated this patient was de novo metastatic, so metastatic at diagnosis. That made a huge impact in their care. If they were locally advanced, then their treatment would likely be neoadjuvant chemotherapy or systemic therapy followed by surgery for a curative intent. But now with the knowledge that the patient is already metastatic, the likelihood of a mastectomy providing value is greatly decreased. And this patient’s plan changed from surgical management to systemic therapy in order to try to control the disease.

The second cohort of patients where the FES-PET trial is active is patients who have had disease that has been treated, and now has for some reason, like an elevated tumor marker or an inconclusive image finding, suspicion for breast cancer recurrence. Here is a patient who has suspicion of a recurrence in the left chest wall. Standard of care FDG-PET to evaluate the extent of disease found a solitary focus in the chest wall. However, the FES-PET unfortunately identified multiple osseous and soft tissue lesions, which were not apparent on the FDG-PET. Thus, the FES-PET evaluating estrogen receptor was much more accurate in identifying the extent of disease than the metabolic tracer FDG.

Now, both of these patients I just described had invasive lobular breast cancer. These tumors are known to be harder to find than the more common ductal malignancy. Lobular breast cancers are molecularly distinct from ductal malignancies. They tend to have lost a gene called CDH1, which encodes for E-cadherin, a cell adhesion molecule. While ductal tumors that have E-cadherin tend to grow in balls of tumors, lobular breast cancer that lacks this adhesion tends to grow out in sheets and lines, providing fewer tumor cells per unit volume of tissue and making it more difficult to detect on imaging studies like mammography, ultrasound, MR, and FDG-PET. These lobular tumors being more difficult to find by current imaging modalities need a new method of evaluating disease extent.

It so happens that lobular breast cancers are almost all estrogen receptor-positive. This estrogen receptor-positive imaging agent, FES, may be a valuable method for evaluating these patients. Indeed, in a retrospective study that needs to be confirmed in a prospective study of patients on clinical trials who underwent both FDG as well as FES-PET, the FES-PET in the patients with lobular breast cancer identified the extent of disease much more accurately than FDG. We are very excited to be evaluating FES-PET in patients with lobular breast cancers as well as other less metabolically active breast cancers. And hopefully, we’ll be able to advance the field in detection of disease for these patients.

Transcript Edited for Clarity