Optimizing Imaging in ER-positive Metastatic Breast Cancer to Improve Clinical Outcomes - Episode 9

Question and Answer Session


Dr Gary Ulaner and Dr Jeremy Force answer questions submitted by attendees of the live webinar discussing the role of various strategies to detect estrogen receptor (ER)-positive breast cancer, with particular focus on the role of 18-F FES-PET imaging in diagnosis and treatment of ER-positive breast cancer.

Jeremy Force, DO: With that, Dr Ulaner and I would like to take some questions and answers. Please do submit those in the Q & A box, so that we can answer them. It looks like there are 2 that I see here. Dr Ulaner, I would like to ask you this one question. Where is the FES-PET [F-18 fluoroestradiol-positron emission tomography] scan available? I’m assuming that means perhaps worldwide; as you mentioned, it is FDA approved in the United States. But what about the rest of the world in case this is a global audience?

Gary Ulaner, MD, PhD: Thanks, Jeremy, and I’d like to say, your 3 cases are textbook examples for FES. In the first, the patient was FES negative, and they essentially did not respond to ER [estrogen receptor]-targeted therapy. The second was FES positive and responded very well to ER-targeted therapy. And the third was FES negative, so you purposely made the decision, don’t use ER-targeted therapy, use something else, which the patient responded so well to. Thus, really classic examples.

Now, the question being, where is FES-PET available? I’ll start within the United States, this is FDA-approved, so this is available at any hospital in the United States that chooses to offer this agent. It takes time for technology to disseminate. Maybe not all medical centers are using FES-PET currently because it’s only recently been FDA approved. But the same thing could’ve been said about FDG [fluorodeoxyglucose] 10 or 15 years ago. It was only used in a few sites initially, and then when people realized how valuable it was, it disseminated, and now it’s available virtually at any hospital that has a PET scanner. FES is available anywhere that wishes to utilize FES in the United States, and I hope there will be a growing number of centers that will be using it. Of course, at academic centers like Dr Force at Duke University, and myself at a tertiary care center, the Hoag Family Cancer Institute, we have it probably a little earlier than many other centers. I expect many others to jump on board and use it just as much as we do in the near future.

As far as worldwide, again, each country will have its own regulatory agencies. FES is approved in the European Union, so it’s available in those countries. Then, I’m afraid I am not so knowledgeable about other areas in the world at the moment. But again, I do expect, as soon as people realize how valuable this is for many potential applications, that it will become more and more available throughout the world.

Jeremy Force, DO: I think that’s a great answer. Looking through some of these questions here, there’s another great question for you, Dr Ulaner. I think this is really an important, short question, will it be covered by insurance?

Gary Ulaner, MD, PhD: This is a great question, which kind of blurs into another question of, do we need both PET scans? The answer is yes, I think we need both, and I think, yes, it will be covered by insurance providers for the appropriate applications. It all comes back to these scans, even though they’re both called PET scans, they are really individual scans. The FDG-PET scan finds metabolism and is predominantly used to evaluate extent of disease, whereas the FES finds estrogen receptor and is used for different applications, I think primarily to help you determine whether you should use ER-targeted therapies. Thus, while the FDG is very good at extent of disease, it doesn’t often help you choose what therapy you should use. And the FES is not going to find some diseases at all. But in the right diseases, like ER-positive breast cancer, it can be very valuable for helping you select what therapies you want. Hence, use the individual studies for the appropriate clinical indications.

Then for insurance coverage, this will come with the appropriate clinical indications. If you’re ordering an FES-PET scan to try to determine extent of disease, it may not be covered. But if you explain to an insurance company in the case of a patient who may be on a first-line ER-targeted therapy and is progressing, and you say, “I want to decide whether I’m going to move to a second-line ER-targeted therapy or if I’m going to use chemotherapy instead.” It’s a very smart use of money to run a single imaging test that can help you determine whether estrogen receptor-targeted therapy is going to be effective. Because if it’s not FES avid, and therefore ER-targeted therapy is not going to be effective, why spend tens of thousands of dollars and waste months of a patient’s time receiving an ineffective therapy? Thus, I think we do need both scans; we need them for their own appropriate indications, and insurance providers will likely pay for them when used appropriately.

Jeremy, let me shoot a question back to you. There is a specific question here asking, what is your approach to a patient who’s ER+ and HER2+ [human epidermal growth factor receptor 2-positive] who develops an ER+, HER2-negative recurrence during anti-HER2–targeted therapy? Should we escalate the ER-targeted therapy arm or add fulvestrant or add your own recommendations for therapy in this particular patient?

Jeremy Force, DO: Yes, that’s an excellent question, and I think that the FES-PET has some clinical utility here, especially since they were receiving an AI [aromatase inhibitor] in that setting. As Dr Ulaner mentioned, if this patient was receiving tamoxifen or fulvestrant, the FES-PET may not be as effective or might not have as much clinical utility. This is a really challenging situation. I think the FES-PET can provide utility, first and foremost, to describe what is the burden of disease. Is that really the only recurrence? I think that would be first off. Secondly, if they had an isolated recurrence, I would try to aggressively approach that in various forms, whether it be SBRT [stereotactic body radiation therapy] and the SABR-COMET study really identified that there can be an overall survival advantage. Granted, there was a paucity of patients with breast cancer in the SABR-COMET study. But it did show that SBRT can provide a benefit in the oligometastatic or oligoprogressive setting.

Thirdly, obtaining an FES-PET to identify the ER negativity would be helpful, but one would question the HER2 status. And that’s where I think an FES-PET may not be helpful in that situation to determine HER2 positivity or negativity, for that matter, because that is not the point of what the FES-PET is providing. In this situation, though, if they have an isolated recurrence, and it’s hormone-positive, HER2- by biopsy, I think an aggressive approach with SBRT, resection, cryoablation, or radiofrequency ablation, followed by an endocrine therapy-focused approach would be pretty reasonable.

Gary Ulaner, MD, PhD: Thanks, Jeremy.

Jeremy Force, DO: Yes. Let me shoot you back a question here. Are there specific precautions for using FES-PET for patients? I think that’s a great question for you, Dr Ulaner.

Gary Ulaner, MD, PhD: Thanks, Jeremy, for that question. In general, imaging agents have very low adverse effects. This isn’t a therapy, per se, that is going to have adverse effects that you need to be very aware of in using in patients who may have borderline organ function. The main precaution to keep in mind is really with tamoxifen and fulvestrant, drugs that bind to the estrogen receptor to have their effect. Those drugs can interfere with the proper results, the proper interpretation of the FES-PET scan. Patients who are using tamoxifen or fulvestrant will need to withdraw from those medications prior to using FES-PET as a diagnostic imaging agent. And for patients with fulvestrant, where they recommend 4 or 5 months of withdrawal, I think this is probably going to exclude using FES-PET in these patients because no one is going to want to wait 4 or 5 months off therapy, in order to get a diagnostic scan. That’s just the unfortunate part of it. You have to keep that in mind.

But as for precaution, there’s very little. These diagnostic agents are very well tolerated with minimal adverse effects. From the FDA approval, they note that less than 1% of patients who undergo FES-PET scans have adverse effects like pain at the injection site, which you can imagine, because there’s an IV [intravenous] catheter in your arm. And less than 1% of patients have changes or alterations in their sensation of taste for about 1 to 2 days. I think in the current climate with COVID-19, it’s important for patients to know because if after their scan, they go home and they can’t taste their dinner, they might be worried that’s being caused by COVID-19, when in reality, it’s being caused as a rare adverse effect of the FES. But other than those 2 minor adverse reactions that have been noted, there are virtually no other adverse reactions, and the studies show they are very well tolerated, and no specific precautions need to be taken with specific patient populations.

Let me ask you, Jeremy, if we can look toward primary treatment where the tumor markers change. There’s a question here, what you do in the instance where the primary tumor doesn’t necessarily match, the tumor markers don’t match what you find subsequently in the patient’s care?

Jeremy Force, DO: Yes, it’s a great question. It’s something that we’re actively studying at Duke University and putting together trials to further investigate this, utilizing the FES-PET as a key component to identifying the estrogen receptor status. I’m assuming that you’re performing primary treatment and then the markers change after surgery, so they may have been getting neoadjuvant therapy, they went to surgery, and then those markers were checked again, and they were indeed nowhormone receptor negative. In those situations, we would offer somebody adjuvant chemotherapy if they didn’t already receive it in the neoadjuvant setting. It could be that that person was getting neoadjuvant endocrine therapy with an aromatase inhibitor. And if the biomarkers changed, I would certainly utilize the FES-PET, first as a way to determine has it spread anywhere else. As Dr Ulaner pointed out nicely, there was the patient who had stage III disease, and the FES-PET depicted that this patient had de novo metastatic disease.

I think the FES-PET will provide clarity to determine the bulk or burden of disease. And if the biomarkers have changed from a primary cancer, I think providing chemotherapy in the adjuvant setting; if this is metastatic disease, which we know that the biomarkers can change not infrequently, I think again, consideration of moving forward with the chemotherapy route would be imperative. The risk-benefit ratio of moving forward with endocrine therapy has been laid out nicely in the literature, that there’s a lack of benefit, and this is already declared itself as basically endocrine-therapy resistant. I think, again, the FES-PET will provide some clarity in that regard.

Dr Ulaner, I would like to ask this question about the processing of bone biopsies. This is a common problem, as you know, that we have in hormone-positive metastatic disease. Can you talk a little about the processing of bone metastases, and will there be any false negatives for estrogen receptor positivity or negativity?

Gary Ulaner, MD, PhD: Thanks, Jeremy, for that question. I’ll preface the answer by saying I’m not a pathologist. They will be the most knowledgeable. But having encountered this problem before, I can give some perspective. In general, the processing for estrogen receptor status, the immunohistochemistry is pretty robust. I’ve seen this be more a problem with HER2 status, where the processing of the bone samples prior to HER2 sampling can cause a false reduction in what we see on the immunohistochemistry. So the HER2 status is false negative, essentially, on the pathology because of the processing of the bone. But I have not heard of that error occurring so commonly with respect to estrogen receptor.

Jeremy Force, DO: Yes.

Gary Ulaner, MD, PhD: If I can hit one question here, this person gets right to the point and asks, why do we need this? We already have ER and PR status, and I think that’s right to the point, a critical question. And the answer being that the immunohistochemistry doesn’t always predict how patients are going to respond to therapy. To go back to this slide, the patient on top and the patient on the bottom are both ER+. They’ve had their immunohistochemistry determined, and they were both estrogen receptor positive. But they have very different results on their FES-PET scan. And that difference, despite the fact that they’re both ER+, the FES-PET is far more predictive in determining whether the patients are going to respond to ER-targeted therapy. Yes, it’s an incredibly valuable tool to have a biopsy and ER and PR immunohistochemistry. But this is a strong example of how the whole-body imaging can help you decide what therapies you want to utilize for your patients and be more accurate in predicting treatment outcome than immunohistochemistry from single sight biopsies.

Jeremy Force, DO: Yes. Dr Ulaner, that was really well said.

We all thank you for your attention and participation tonight. On behalf of Dr Ulaner and myself, I would like to thank you for joining us in the OncLive® webinar on radiopharmaceuticals-based imaging in breast cancer. We hope you found this discussion to be informative and valuable in the treatment of your patients with breast cancer. We thank you for your time.

Gary Ulaner, MD, PhD: Thank you.

Transcript Edited for Clarity