Abstract Background: Assessing invasive lobular carcinoma (ILC) with standard-of-care (SOC) imaging, such as 18F-fluorodeoxyglucose (FDG) PET-computed tomography (CT), is challenging. In May 2025, National Comprehensive Cancer Center Network guidelines added FES PET for recurrent/metastatic ILC staging. However, perceptions of the value added by FES PET to SOC imaging may vary, as only small ILC cohorts have been published. We evaluated FES PET’s clinical utility in the largest-studied cohort, to our knowledge, of ILC pts who have undergone FES PET. Methods: We identified all ILC pts who had an FES PET PET-magnetic resonance (MR) or PET-CT) between April 1, 2021, and May 1, 2025, at Mayo Clinic. Clinical and radiological data, including indications and management (mgmt) changes related to pts’ first FES PET, were obtained from clinical records. FES and SOC FDG PET were compared. Data were summarized with descriptive statistics. Results: 102 female pts were included: 88% White and 4.9% Black. Median age at initial breast cancer (BC) diagnosis was 57 (range, 36-79). At initial ILC diagnosis, most tumors were strongly estrogen receptor (ER) positive. Highest tumor grade was 1 in 25% of pts and 2 in 57%, with grade not documented in 19%; none had documented grade 3 ILC. Initial clinical prognostic stage was as follows: 26% stage 1, 21% stage 2, 10% stage 3, and 16% stage 4. At the time of FES PET, 37% had biopsy-confirmed metastatic ILC at the time of FES PET. The most common indications for FES PET were (re)staging ILC (49%), detecting suspected metastatic/recurrent BC (30%), and evaluating rising tumor markers like CA 15-3 or CA 27.29 (15%). 16% of pts were upstaged due to the FES PET result: 14 pts to stage 4 and 2 pts to stage 3. FES PET led to a mgmt change in 38 pts (37%), for whom the most common FES PET indications were (re)staging ILC (21 pts), detecting suspected recurrent/metastatic BC (11 pts), and detecting ER expression when biopsy was not feasible/nondiagnostic (7 pts). 19 scans (50%) led to a systemic therapy (tx) decision, 10 (26%) to a biopsy, 4 (11%) to additional imaging like MRI, 3 (8%) to locoregional tx, and 2 (5%) to a non-oncologic specialty referral to evaluate a suspected new metastasis. 11 pts had stage 4 BC pre-FES PET; their FES PET was ordered primarily for restaging (5 pts) or detecting ER expression (5 pts). Notably, of the 19 pts with a systemic tx-related change, 4 began a triple-negative BC regimen due to low FES uptake on the scan. Of the 15 pts who had FES PET to evaluate a rising tumor marker, a direct change in systemic tx occurred in 2 pts. 63/102 pts (62%) had FDG PET-CT prior to FES PET. Of these, 57% had discordant FDG and FES PET results. 39% had a higher number of avid metastatic lesions on FES PET as compared to FDG PET, primarily in the bone (8 pts) and lymph nodes (4 pts). 25% had bone, nodal, or soft tissue metastatic lesions that were FDG but not FES avid. 13 pts had FES PET-MRI; 9 of these had a prior FDG PET-CT. 2 PET-MRI pts had FES-avid metastatic lesions in unusual sites (brain, peritoneum) that were not FDG avid. Among the 38 pts with a mgmt change due to their FES PET result, 63% had prior FDG PET; 32% of the 38 pts had FES-avid metastatic lesions that were not seen on FDG PET, and 8% had FDG-avid but not FES-avid lesions. Conclusions: FES PET was useful for evaluating not only stage 4, but also early-stage ILC, with 1/3 of pts with an FES PET-driven mgmt change having early-stage BC. FES PET was most helpful for ILC (re)staging, detection of suspected recurrent/metastatic BC, and detection of ER expression when biopsy was not feasible/nondiagnostic. FES PET added clinically meaningful information beyond SOC imaging, with detection of FES-avid but not FDG-avid metastatic lesions in 1/3 of pts with an FES PET-driven mgmt change. Notably, FES PET-MRI demonstrated potential superiority over FDG PET in identifying atypical ILC metastases. Citation Format: T. Pai, C. Bullock, N. Wiest, E. Parent, P. Advani. Clinical utility of 18F-fluoroestradiol positron emission tomography (FES PET) in patients (pts) with lobular breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD9-09.
Pai et al. (Tue,) studied this question.