Refined Breast Imaging Strategies Improve Cancer Detection, Clarify Staging, and Augment Care

Advances in breast cancer imaging, particularly estrogen receptor (ER)–targeted 18F-fluoroestradiol (FES)–PET/CT scans, are improving diagnostic precision and informing complex treatment decisions across disease stages, according to Megan Kruse, MD.

“[FES-PET/CT] allows us to look at the body in a completely different way [compared with other imaging modalities], particularly for cancers we know [can be] ER positive,” Kruse said in an interview with OncLive®.

In the interview, Kruse discussed the use of various imaging modalities in breast cancer management and emphasized the role of FES-PET/CT in identifying ER presence, which is useful for clarifying uncertain findings and guiding subsequent treatment decisions. Kruse also highlighted the importance of breast MRI for lobular breast cancer to avoid disease underestimation. Finally, she suggested the future potential for FES-PET/CT in early-stage breast cancer detection.

Kruse is a breast medical oncologist at Cleveland Clinic in Ohio.

Want to learn more about FES-PET/CT developing role in breast cancer? Hear Kruse’s insights synthesized with those from Sophia O’Brien, MD, of Penn Medicine, in this podcast episode about the importance of collaboration between medical oncologists and nuclear medicine physicians when optimizing the use of FES-PET/CT in breast cancer management.¹ Additionally, read Jason Aboudi Mouabbi, MD, of The University of Texas MD Anderson Cancer Center in Houston, dive deeper into the role of FES-PET/CT for lobular breast cancer detection.²

OncLive: What imaging modalities are currently used in clinical practice for breast cancer diagnosis?

Kruse: In breast cancer, typically, as we’re diagnosing the primary breast cancer in the breast itself, many patients will receive diagnostic mammograms and ultrasounds, and those images typically will give us an idea of the extent of the cancer in the breast. They often give us an idea of whether there is lymph node involvement, particularly in the underarm or axillary area. Additionally, for many patients who are considering surgical management upfront rather than medical management, we may consider a breast MRI to get a better-defined picture of how big the breast mass is, where in the breast it’s located, and how that might affect what surgery a patient chooses.

Furthermore, in advanced breast cancer, we’re worried that the cancer may have already spread to a different place in the body. This may be in a patient with presumed early-stage breast cancer before they start surgical management or medical management, or it could be for a patient with a history of breast cancer with symptoms that suggest that the breast cancer has spread somewhere else in the body. The imaging that we typically would use [in those patients] would be conventional CT scans of the body, which would usually include the chest, abdomen or pelvis, often with intravenous contrast. Then, for certain patients, depending on the type of breast cancer and the way the symptoms are presenting, you might also consider an 18F-fluorodeoxyglucose [FDG]–PET/CT scan using a fluorinated glucose compound to look for metabolic activity in the body that would be suggestive of cancer being present in another organ outside the breast.

Lastly, for patients with brain symptoms, [which can sometimes be] headaches or double vision, we would consider adding a brain MRI. [Brain MRI] is evolving in our world a bit. Historically, we have not done brain MRIs off the bat, even for patients with known metastatic breast cancer.

But many agents we use for medical management of breast cancer do get into the brain. It may be helpful to know that information about a patient before they start treatment, because it may influence which medical treatment you select. I think about this particularly for patients with HER2-positive breast cancer.

How can breast cancer imaging modalities help with treatment decision-making?

When you’re deciding on a treatment strategy, you want to use whatever [imaging modality] you think will give you the best delineation of where the cancer is and help you identify whether the cancer is somewhere you don’t suspect. [Identifying where the cancer is] may take you down a different road of treatment. I consider this primarily for patients with locally advanced breast cancer, where we know the breast mass might be rather large, or there’s suggestion of axillary lymph node involvement. When we look for distant metastatic disease, if we find disease that has spread outside the breast or those regional lymph nodes, that may make local therapy with breast surgery or radiation less important for that patient than receiving medical therapy first.

[When] making plans for local therapy, I’m trying to be selective about which patients we order imaging of the whole body for. I often consider breast MRI, particularly in patients with lobular breast cancer who are doing surgical decision planning. On conventional mammogram and ultrasound, the extent of the size of these lobular tumors may be underestimated.

We get a better sensitive image when we use breast MRI for patients with lobular breast cancer. That’s particularly important in patients with lobular breast cancer who might be deciding on breast conservation, for example, and undergoing a lumpectomy. If we get a breast MRI and the tumor looks bigger than we originally expected on mammogram, we can make a treatment change where a patient may decide to go ahead with mastectomy, or we as the physician team may recommend mastectomy.

What differentiates FES-PET/CT from other imaging modalities?

FES-PET/CT is an interesting imaging modality that looks at ER presence in tumors in the body. With other imaging modalities like CT scans and bone scans, [we look for] the presence of changes that anatomically alter the organ appearance. We may see a mass where there shouldn’t be one in the lung or liver, or we may see lytic or sclerotic changes in a bone that suggest a mass-forming area within the bone. With FDG-PET/CT, which is our traditional PET scan that we’ve used in breast cancer for years, you’re assessing metabolic activity.

[However,] FES imaging is using a fluorinated estradiol to attach to ERs on areas of the body that express it. We know this tracer will show up in normal sites of metabolism, like the liver and the gastrointestinal and genitourinary tracts. It can also light up in the uterus, where we know there are normal ERs.

But in other areas, like bone, lung, and liver, where you wouldn’t expect there to be any ERs present normally, should you find ERs with FES-PET/CT, you have [evidence] that there is ER-expressing breast cancer present. Or, in times where we’re not sure what an imaging finding means, this [modality] may give us information or clues about what that imaging finding may represent.

What are the current roles for FES-PET/CT in breast cancer?

FES-PET/CT is helpful in cases where we have uncertainty. That’s where it has its best role at present. If we have imaging that has an uncertain finding in a patient with a known history of breast cancer, or even in a patient who was recently diagnosed, FES-PET/CT can help us determine what that uncertain imaging finding on another modality might be.

That’s most influential when a patient may have an area of concern that is difficult to biopsy. Many patients with breast cancer may have relatively small areas of concern on imaging. They may have areas in the bone that are hard to reach, or areas in other organs that are close to blood vessels. If that’s the case, and it would be dangerous or impossible to do a biopsy, [this is where] FES-PET/CT can help you.

If you do the imaging and find [a site] that’s ER positive, that gives you a good idea that it is cancer, because it’s hard to explain that any other way. There are some false positives you can get with FES-PET/CT, particularly in the lung. If a patient has had prior radiation, radiation pneumonitis might show some ER uptake. You might see [a false positive] if a patient has interstitial lung disease, or for other reasons. You have to use the patient’s clinical history as you’re interpreting the FES-PET/CT, but it can be a good tie breaker imaging modality when you have other findings that you’re not sure what to make of.

The other clinical situation where I think [FES-PET/CT] is helpful is if you have a patient who you’re already treating for breast cancer, particularly metastatic breast cancer, and they’ve been receiving therapy that may be estrogen specific, which is all endocrine therapies. You may be trying to make a decision about which way you go with treatment moving forward. Do you use another estrogen-based therapy? Do you go to chemotherapy?

If you use FES-PET/CT, you might be able to tell, based on the amount of ER present, whether that patient would have a good response to further anti-estrogen therapy. This is helpful in our current path of treatment, where most patients with metastatic hormone receptor–positive breast cancer would be receiving first-line therapy with an aromatase inhibitor. If they’re progressing on that aromatase inhibitor, you can get this FES-PET/CT scan that may allow you to say that if there is ER present, they should go on to that second line endocrine therapy. Or, if there seems to be low-level ER or no ER present, perhaps you go down a different road of either targeted treatment or chemotherapy.

There are some caveats there. If a patient is already receiving an ER blocker like tamoxifen [Nolvadex], an oral selective ER modulator, an oral selective ER degrader [SERD], or the intramuscular SERD fulvestrant [Faslodex], these agents will bind to that ER where the fluorescent estradiol will be trying to bind as well. If a patient is receiving one of those drugs, you may get a falsely negative scan. There are washout periods for each of these drugs that a patient may be receiving that affect the ER. That’s important since SERDs, particularly oral SERDs, are coming to the metastatic breast cancer treatment paradigm, and we’ll be seeing more of those patients as our clinical practice continues.

What potential future roles might FES-PET/CT serve in breast cancer beyond its current usage?

One area where FES-PET/CT scans could be useful moving forward would be in better delineating the extent of cancer in the early-stage breast cancer setting. Right now, the number of early-stage breast cancers—meaning stage I or II that I would order an FES-PET/CT on, is limited. If I am ordering FES-PET/CT in the early-stage setting, it would more likely be for a patient with stage III breast cancer, where I’m looking for distant or metastatic disease. But many of us are wondering, especially in cancers that are high ER expressing and potentially have low metabolic activity, like invasive lobular cancers, whether we could use FES-PET/CT to get a better sense of the amount of cancer in the breast, as well as in regional lymph nodes. This would be helpful for treatment planning with surgery.

With how helpful MRI is, FES-PET/CT may be the next stage of that evolution of how we better surgically plan for patients. For some cancers, I’m not sure whether we’re staging them appropriately from the beginning. I’m certain there are some presumed stage I or II cancers, particularly lobular cancers, that may have small-volume metastatic disease from the beginning that we can’t detect with conventional imaging.

My suspicion is that if we were using [an imaging modality that was] more systematically ER-driven like FES-PET/CT, we might pick up on those cancers earlier. That may be disappointing to a patient, because it would take them out of the curative-intent setting and into the treatment of metastatic breast cancer, but it could save a patient from a lot of morbidity from a surgical procedure that ultimately they wouldn’t end up benefiting from. Refining how we use this imaging technology outside the metastatic setting is the next logical place to go in clinical development.

References

1. Kruse M, O’Brien SR. Breast imaging advances emphasize the importance of patient-focused nuclear medicine collaboration: with Megan Kruse, MD; and Sophia O’Brien, MD. February 27, 2026. Accessed March 25, 2026. https://www.onclive.com/view/breast-imaging-advances-emphasize-the-importance-of-patient-focused-nuclear-medicine-collaboration-with-megan-kruse-md-and-sophia-o-brien-md
2. Wahner A. FES-PET/CT guides staging and endocrine therapy decision-making in lobular breast cancer. February 17, 2026. Accessed March 25, 2026. https://www.onclive.com/view/fes-pet-ct-guides-staging-and-endocrine-therapy-decision-making-in-lobular-breast-cancer