18F-fluoroestradiol (FES)–PET/CT has emerged as a highly sensitive imaging tool to improve lobular breast cancer detection and more accurately stage disease and predict response to endocrine therapy, according to Jason Aboudi Mouabbi, MD.
“[If a patient has] stage I, II, or III lobular cancer and is worried about metastatic disease, you can [do FES-PET/CT],” Mouabbi said in an interview with OncLive®. “Any time the treating oncologist worries that there might be metastatic disease per the National Comprehensive Cancer Network [NCCN] Guidelines, the patient can get FES-PET/CT.”
In the interview, Mouabbi discussed the challenges associated with diagnosing lobular breast cancer, which doesn’t form solid masses, making it difficult to detect with standard imaging. He highlighted that FES-PET/CT imaging, which uses a radioactive fluoroestradiol molecule, offers promising sensitivity for detecting lobular breast cancer compared with standard PET scans. Mouabbi also noted areas of clinical practice where FES-PET/CT is particularly useful, such as for assessing metastatic disease and predicting response to endocrine therapy.
Mouabbi is an assistant professor in the Department of Breast Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.
OncLive: What differentiates lobular breast cancer from ductal breast cancer in terms of diagnosis and overall prognosis?
Mouabbi: Lobular breast cancer is unique [because it] tends not to form those solid masses that we used to think about when we thought about cancers. One of the hallmarks of lobular disease is the loss of the anchoring protein E cadherin. When a disease does not have that anchor, those cells lose their stickiness, so they don’t [stick] together, and they don’t attach to anything around them.
They are cells in suspension. They are floating around. That’s why they tend not to form those masses or distort the architecture of any of the organs they get involved in.
Eventually, the body starts laying down scar tissue around [the cancer] to try to contain it, and that’s when it sometimes gets problematic, and when sometimes [a patient] can feel it. But otherwise, the cancer itself is discohesive. It doesn’t form giant tumors.
Due to this, imaging of lobular disease is tough because imaging relies on the size of a mass. Usually, anytime the size is below 1 cm, the imaging is not good. Here lies the problem. Lobular breast cancer is not going to form a tumor that is even 1 cm. All the current standard-of-care [SOC] imaging [tools] are challenging to use for lobular breast cancer. That’s why we need to find innovative ways to look at lobular breast cancer.
How does FES PET differ from standard imaging modalities regarding its ability to detect lobular tumors?
FES-PET/CT Use in Lobular Breast Cancer: Key Points
- Lobular breast cancer is uniquely difficult to detect with standard imaging because it lacks the anchoring protein E-cadherin, causing cells to remain discohesive rather than forming the solid masses that standard scans rely on for identification.
- FES-PET/CT provides a superior diagnostic approach for lobular breast cancer by targeting the ER rather than metabolic activity, resulting in a sensitivity rate of approximately 90% compared with 45% to 50% with SOC imaging modalities.
- FES-PET/CT is a critical tool for staging distant metastatic disease and predicting a patient’s response to endocrine therapy, particularly when traditional biopsies are inconclusive or the cancer shows low positive ER expression levels.
Anytime you have a target and a well-known ligand to that target, you can leverage [that ligand] to try to see the target. Lobular breast cancer is addicted to estrogen. The estrogen receptor [ER] is usually highly expressed in lobular breast cancer, and we can leverage that.
We have a target of the ER inside lobular cancer cells. [The ER is] a target for estrogen, so we can piggyback onto the estrogen a radioisotope, so where it binds, it can light up, and we can see it. That’s the best way, at this point, to look at lobular breast cancer.
The technology is FES. It’s an estrodial molecule, [a form of] estrogen, and there is a fluorine atom added to it that’s radioactive. We can detect that emission and see [the target].
The technology is a PET scan, but the radioisotope is FES, so this is different than a regular PET scan. Regular PET scans use fluorodeoxyglucose [FDG]. FDG uses the same fluorine atom that we use [with FES-PET/CT], but we piggyback on the glucose molecule.
Regular PET scans leverage the idea that cancers are more metabolically active than healthy cells, so they will try to hoard all the sugar you give them. By doing that, they light up. Lobular breast cancer is not that metabolically active, so it’s not going to light up on a regular PET scan. However, when you give FES-PET/CT, [which uses] estradiol instead of glucose, then [the lobular cancer] lights up, and you can see it.
In studies, we evaluated SOC imaging, with regular CT scans, bone scans, and regular FDG-PET/CT scans. When we compared [these] with FES-PET/CT, we doubled the detection [rate with FES PET]. The sensitivity rate is approximately 90% when you use FES-PET/CT to detect lobular disease, whereas with the other SOC imaging [modalities, it was] only approximately 45% to 50%. We’re not at 100%. No test is foolproof, but [FES-PET/CT is] much better than the SOC [imaging strategies].
What factors go into selecting FES-PET/CT vs FDG-PET/CT as the preferred imaging strategy for a given patient?
FES-PET/CT is not meant to monitor treatment response. FES-PET/CT is meant to be conducted at one point in time to give us an answer [for a given question]. If you’re [assessing] early-stage [disease], you want to see: Has the cancer already metastasized to a distant location? In the advanced setting, you can use [FES-PET/CT] for multiple reasons.
I was part of the group that the Society of Nuclear Medicine and Molecular Imaging hired to [create] the appropriate use criteria for FES-PET/CT in breast cancer. What indications are there for us to use it? These are important. If you’re trying to diagnose primary breast cancer, or you’re trying to stage the tumor in the breast and the lymph node, that is not an appropriate use of this technology. When you are trying to stage distant [disease] outside of the breast and the regional nodes, then it can be appropriate to use [FES-PET/CT].
For lobular breast cancer staging, the use of [FES-PET/CT] is appropriate. One of the areas where it can be useful is, let’s say you do a biopsy to check if a site is metastatic, and you cannot get some information, like biomarkers such as ER; this is common when we do bone biopsies. When we do bone biopsies, because of the decalcification process, sometimes we kill the tissue, so we cannot rely on the biomarker analyses anymore. [FES-PET/CT] technology can be used instead of the biopsy, or in conjunction with the biopsy, to see if a lesion is hormonal or nonhormonal. That’s big because it gives a big implication for treatment.
The other [useful role for FES-PET/CT] is if there is a lesion that you cannot biopsy. A common example here is a brain lesion. We don’t like to do brain biopsies. Sticking a needle in the brain is never an action we take lightly, because there are so many different things close to each other, and [intervening in those areas] can affect cognition, movement, etc. If a patient with metastatic breast cancer now has a lesion in their brain, you want to know whether it’s hormonal. You can [use FES-PET/CT for that]. [It can] tell you whether it’s ER positive. Then you can do treatment.
But one of the most appropriate uses of that technology is that it’s the only tool we currently have that can predict response to endocrine therapy plus or minus targeted therapy. The common scenario here is: you have a patient who has metastatic breast cancer, you do a biopsy, and the [ER expression rate] is low positive, like 5%. This is a dilemma for the treating oncologist: Is this cancer truly hormonal? Five percent is low. Should we give the patient a hormonal treatment, or should we treat them like [they have] triple-negative breast cancer [TNBC] and choose chemotherapy, immunotherapy, or an antibody-drug conjugate [ADC]? This technology can give you the answer.
Historically, we said that FES avidity [was defined as an SUVmax of] 2 and above, for simplicity, but actually, any SUVmax of 1.8 and above at this point predicts response to endocrine therapy, meaning the cancer is hormonal and corresponds to an anti-hormonal agent.1 Anything below that [level should be] managed like TNBC. This is one of the best uses for that technology.
Another common scenario is if a patient progresses on a first-line hormonal agent, and you want to see whether they would benefit from another hormonal line of therapy, or if you should abandon ship and [choose a treatment like] chemotherapy or an ADC. Here, FES-PET/CT can be useful, because you can assess the avidity of those lesions. If [they have an SUVmax of] 1.8 or above, that’s one of the best predictors that a patient would benefit from a second line of hormonal therapy.
There are specific [FES-PET/CT] use criteria you can use. We were happy that the NCCN Clinical Practice Guidelines in Oncology for invasive breast cancer [now] mention FES-PET/CT and lobular breast cancer in the same sentence.2 Any time you are suspecting metastatic disease, you can get FES-PET/CT staging for your patient. We keep this in the hands of the treating physician.
References
- Xu Y, Yao R, Hao Z, et al. [18F]F-FES PET for diagnosis, staging, and endocrine therapy prediction in ER-positive breast cancer: a systematic review and meta-analysis. EJNMMI Res. 2025;15(1):17. doi:10.1186/s13550-025-01205-x
- NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 1.2026. January 16, 2026. Accessed February 17, 2026. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
