Abstract PD4-10: 18F-fluoroestradiol (FES) and 18F-fluorodeoxyglucose (FDG) PET imaging in staging extent of disease in metastatic lobular breast cancer
Authors: Manohar PM , Peterson LM , Wu V , Jenkins IC , Novakova-Jiresova A , Specht JM , Link JM , Krohn KA , Kinahan PE , Mankoff DA , Linden HM 
Published: May 2019

Abstract
Background: The histology and pattern of spread in lobular breast cancer has presented challenges in estimating extent of disease and identifying treatment options. 18F-FES is an estrogen analogue PET imaging tracer which measures tumor ER expression at multiple tumor sites simultaneously and predicts response to endocrine therapy. We analyzed FES-PET and FDG-PET SUV uptake in patients with metastatic lobular and ductal carcinoma to identify sites of tumor and responsiveness to therapy.
Methods: We retrospectively reviewed FES and FDG SUV uptake between ER+ lobular (n = 36) and ductal (n= 173, including 6 men) metastatic breast cancer patients enrolled in various institutional studies. Up to 3 lesions in each patient were evaluated by FES SUVmax and/or FDG SUVmax for a total of 475 lesions in FES images and 462 lesions in FDG images. Classification into three categories (low FDG, high FDG/high FES, and high FDG/low FES) was generated using recursive portioning with 5-fold internal cross validation. Using a Pearson Chi-squared test, we compared degree of uptake in FES and FDG between lobular and ductal carcinomas. We used linear mixed effects model to assess association of FES SULmean3 (Lean body mass adjusted SUV) and FDG SULmean3 with histology. Overall survival (OS), from time of FES-PET scan to death, and progression free survival (PFS) was evaluated between classification groups in both histologies using Kaplan-Meier curves and Cox model.
Results: In patients with metastatic breast cancer, 72 patients had low FDG, 96 had high FES/high FDG, and 41 with high FES/low FDG. Lobular lesions tended to have a higher proportion of patients in the risk group with lower FDG (42% vs 33%) and a lower proportion in the risk group with high FDG/low FES (11% vs 21%) but the difference was not statistically significant (p = 0.32). Mean (range) FES SULmean3 and FDG SULmax3 respectively for ductal was 1.38 (0.10, 6.7) and 3.17 (0.88, 12.26) and for lobular was 1.42 (0.34, 3.43) and 3.13 (1.04, 13.87). There was no significant difference between in FES SULmean3 and FDG SULmax3 between histologies. Following FES-PET imaging, patients with lobular carcinomas and low FDG demonstrated a higher median survival time (7.7 years) compared to high FDG/low FES (4.3 years) and high FDG/high FES (2.6 years). Similarly, patients with ductal carcinomas and low FDG had an improved median survival time (5.6 years) compared to both high FDG/high FES (2.9 years) and high FDG/low FES (2.5 years). However, the interaction between histology and the FDG/FES classifications was not significant (p = 0.86). Across a variety of tumor sites, lobular histology can be detected by both FES and FDG with no difference between the imaging modalities.
Conclusions: In the metastatic setting, quantitative FES and FDG can be used to discriminate indolent and aggressive phenotypes in both lobular and ductal breast cancer. A greater proportion of lobular carcinoma lesions had higher FES/lower FDG and would be anticipated to be more sensitive to endocrine therapy. Further prospective trials are needed to confirm the utility of FES to stage extent of disease in metastatic breast cancer.
Citation Format: Manohar PM, Peterson LM, Wu V, Jenkins IC, Novakova-Jiresova A, Specht JM, Link JM, Krohn KA, Kinahan PE, Mankoff DA, Linden HM. 18F-fluoroestradiol (FES) and 18F-fluorodeoxyglucose (FDG) PET imaging in staging extent of disease in metastatic lobular breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-10.