Abstract Background: Invasive lobular cancer (ILC) poses diagnostic challenges due to its diffuse growth pattern, often leading to upstaging at surgery and the potential for suboptimal initial management. 16α-18F-fluoro-17β-estradiol positron emission tomography (FES-PET) has shown utility in assessment of estrogen receptor (ER) positive disease. Given ILC’s diagnostic complexity, FES-PET may enhance the initial staging and management of newly diagnosed locally advanced ILC. This case series explores FES-PET’s potential role in optimizing the management of newly diagnosed locally advanced ILC. Methods: An institutional retrospective case series of 6 patients with newly diagnosed ILC between 4/2024-4/2025 was conducted. Three patients underwent FES-PET which altered or confirmed management, and 3 patients did not undergo FES-PET but were upstaged at the time of surgery. Data on patient demographics, standard of care (SOC) imaging (e.g. mammogram, MRI, CT C/A/P, bone scan and/or FDG-PET), FES-PET findings, pre-FES-PET management plans and post-FES-PET management plans were extracted from the medical records. Results: In Case 1 (ER: 100%), FES-PET detected occult supraclavicular (SCL) nodal involvement (SUV: 3.3) and confirmed residual chest wall (CW) disease (SUV: 5.4) post-neoadjuvant chemotherapy (NAC) and mastectomy, prompting extended radiation volumes and a 1000 cGy in 5 fraction boost to the SCL nodes and CW. In case 2 (ER: 95%), FES-PET detected osseous metastatic disease (SUV: 3.5) not detected on SOC imaging, shifting management to systemic therapy. In case 3 (ER: 100%), FES-PET confirmed no metastatic disease after completion of adjuvant chemotherapy for pT3N3a locally advanced disease; therefore, definitive local therapy with radiation was supported. Patients in cases 4-6 without FES-PET were significantly upstaged at the time of surgery despite SOC imaging; Case 4: (ER: 100%, cT2N1M0, pT3N3a), Case 5: (ER: 100%, cT1N0M0, pT2N2a), Case 6: (ER: 100%, cT1N1M0, pT2N3a), suggesting that FES-PET could have guided initial management. Discussion: FES-PET altered radiation dose/volumes (Case 1), shifted treatment to systemic therapy (Case 2), and confirmed initial treatment plan with local therapy (Case 3). In cases 4-6, FES-PET may have more accurately detected the extent of primary and nodal disease, thereby preventing upstaging at the time of surgery. Recent investigations have demonstrated the potential superiority of FES-PET in detecting ILC in the recurrent or metastatic setting. As a result, FES-PET is now recommended during the work-up for recurrent or metastatic ILC in the NCCN guidelines. However, there is limited data exploring the role of FES-PET in newly diagnosed locally advanced ILC. Unlike FDG-PET, FES-PET minimizes treatment-related inflammatory changes, potentially improving diagnostic accuracy. Future prospective clinical investigations are warranted to validate FES-PET’s role in in the management and outcomes for locally advanced invasive lobular cancer. Citation Format: A. Crum, A. Oliver, M. Harrell, B. Facer, T. Andraos, J. Eckstein, R. Young, S. Jhawar, S. Beyer. The impact of 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) on the staging and management of invasive lobular carcinoma (ILC) of the breast: A Case Series 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 PS1-06-21.
Crum et al. (Tue,) studied this question.