BACKGROUND: Patients with ER+ breast cancer may have a recurrence risk of aggressive disease. While clinical evidence suggests that ER+ tumors are responsive to endocrine therapy, up to one-third of patients with early-stage ER+ disease may not respond to endocrine therapy. Tumor biologic factors such as ER functionality, cell proliferation, and molecular traits may influence endocrine treatment responsiveness and long-term recurrence risk. More comprehensive tools are needed to depict the primary breast tumor. [18F]fluoroestradiol (FES) is a radiotracer developed for positron emission tomography (PET) imaging of ER status. We used FES with a high-resolution dedicated breast PET (dbPET) to quantify ER expression in primary ER+ tumors and assessed the relationship between FES uptake and tumor characteristics. METHODS: With IRB approval, patients with biopsy-proven ER+/HER2- breast cancer were imaged using dbPET with 5 mCi of FES before treatment. FES uptake (SUVmax, SUVmean, and SUVpeak), background parenchymal uptake (BPU), tumor uptake volume (TUV), and tumor to background ratio (TBR) were calculated. Background values (SUVbkg) were obtained from the normal region of the ipsilateral breast. Lesions with background-corrected SUVmax 2 times higher than SUVbkg were considered FES avid. Tumor size (longest diameter) was measured by MRI. The histologic subtype, ER expression, tumor grade, and Ki67 were obtained from core biopsies before treatment. Ki67 was dichotomized to low and high using a 20% cutoff. Spearman’s rank correlation was used to assess the correlation between FES uptake and tumor size. Differences between FES uptake, histologic subtype, and Ki67 were compared using a Wilcoxon rank-sum test. RESULTS: 19 treatment-naïve patients were included in this analysis as part of an ongoing study. Patient and tumor characteristics are listed in Table 1. While all patients had ER positivity >90% by immunohistochemistry (IHC), we observed varying FES avidity in ER+ breast cancers, with 14 FES avid and 5 non-FES avid lesions. There was a statistically significant difference between FES avid vs. non-avid lesions measured by all uptake metrics except BPU. FES uptake in invasive ductal carcinoma was similar to invasive lobular carcinoma. FES uptake correlated with tumor size, with the highest correlation ρ = 0.58, 95% CI (0.17, 0.84), p=0.012, detected in TUV. FES uptake was associated with Ki67, with all uptake metrics except BPU showing a statistically significant difference between high and low Ki67 expression (Table 2). CONCLUSION: We found that not all lesions that were highly ER+ by IHC were FES avid. FES-dbPET captures information from the entire tumor, providing a more comprehensive assessment of functional ER status than IHC of a limited tumor sample. Moreover, FES uptake correlates with tumor size and cell proliferation. This is an ongoing study; additional data may help to guide endocrine therapy decisions. Future studies with a larger cohort are planned to assess the relationship between FES uptake and tumor grade and molecular risk profiles.

Table 1.

Patient and tumor characteristics

CharacteristicsNo. of patients
Total N=19
Age (median (IQR)) 56.0 (21.5) 
Pre-menopausal 
Post-menopausal 12 
Histologic subtype  
Invasive ductal carcinoma (IDC) 
Invasive lobular carcinoma (ILC) 13 
Tumor size (N=18) (MRI LD (cm), median (IQR)) 3.2 (4.1) 
Tumor grade  
13 
Ki67  
Low 12 
High 
Unknown 
FES  
Non-avid 
Avid 14 
CharacteristicsNo. of patients
Total N=19
Age (median (IQR)) 56.0 (21.5) 
Pre-menopausal 
Post-menopausal 12 
Histologic subtype  
Invasive ductal carcinoma (IDC) 
Invasive lobular carcinoma (ILC) 13 
Tumor size (N=18) (MRI LD (cm), median (IQR)) 3.2 (4.1) 
Tumor grade  
13 
Ki67  
Low 12 
High 
Unknown 
FES  
Non-avid 
Avid 14 

Table 2.

Summary of baseline FES uptake values

Tumor Size (cm)FES AvidityHistologic SubtypeKi67
Spearman CorrelationAvid vs. Non-avidILC vs. IDCHigh vs. Low
ρ (95%CI)P-valueMedian Diff (95%CI)P-valueMedian Diff (95%CI)P-valueMedian Diff (95%CI)P-value
SUVmax 0.51 (0.054, 0.79) 0.031 8.02 (3.55, 11.9) 0.001 0.187 (-8.04, 6.32) 0.97 6.38 (2.36, 11.6) 0.017 
SUVmean 0.31 (-0.18, 0.68) 0.204 2.42 (1.47, 3.49) 0.001 -0.477 (-1.96, 1.37) 0.57 1.61 (0.81, 2.77) 0.028 
SUVpeak 0.46 (-0.0053, 0.76) 0.053 3.16 (1.42, 5.2) 0.003 -0.583 (-3.76, 2.61) 0.63 3.16 (1.32, 4.66) 0.013 
BPU -0.09 (-0.53, 0.39) 0.723 -0.33 (-1.25, 0.46) 0.379 0.226 (-0.58, 1.19) 0.40 -0.49 (-1.49, 0.28) 0.122 
TUV (cm30.58 (0.15, 0.82) 0.012 5.45 (1.09, 12.5) 0.005 -2.82 (-12.5, 4.06) 0.40 5.9 (0.98, 12.66) 0.021 
TBR 0.5 (0.047, 0.79) 0.033 3.48 (2.2, 13.5) 0.001 -0.295 (-11.9, 7.42) 0.90 10.2 (1.47, 13.49) 0.028 
Tumor Size (cm)FES AvidityHistologic SubtypeKi67
Spearman CorrelationAvid vs. Non-avidILC vs. IDCHigh vs. Low
ρ (95%CI)P-valueMedian Diff (95%CI)P-valueMedian Diff (95%CI)P-valueMedian Diff (95%CI)P-value
SUVmax 0.51 (0.054, 0.79) 0.031 8.02 (3.55, 11.9) 0.001 0.187 (-8.04, 6.32) 0.97 6.38 (2.36, 11.6) 0.017 
SUVmean 0.31 (-0.18, 0.68) 0.204 2.42 (1.47, 3.49) 0.001 -0.477 (-1.96, 1.37) 0.57 1.61 (0.81, 2.77) 0.028 
SUVpeak 0.46 (-0.0053, 0.76) 0.053 3.16 (1.42, 5.2) 0.003 -0.583 (-3.76, 2.61) 0.63 3.16 (1.32, 4.66) 0.013 
BPU -0.09 (-0.53, 0.39) 0.723 -0.33 (-1.25, 0.46) 0.379 0.226 (-0.58, 1.19) 0.40 -0.49 (-1.49, 0.28) 0.122 
TUV (cm30.58 (0.15, 0.82) 0.012 5.45 (1.09, 12.5) 0.005 -2.82 (-12.5, 4.06) 0.40 5.9 (0.98, 12.66) 0.021 
TBR 0.5 (0.047, 0.79) 0.033 3.48 (2.2, 13.5) 0.001 -0.295 (-11.9, 7.42) 0.90 10.2 (1.47, 13.49) 0.028 

Citation Format: Ella F. Jones, Deep K. Hathi, Julissa Molina-Vega, David C. Newitt, Courtney Lawhn-Heath, Kimberly M. Ray, Bonnie N. Joe, Diane Heditsian, Susie Brain, Rita A. Mukhtar, A. Jo Chien, Hope S. Rugo, I-SPY 2 TRIAL Consortium, I-SPY 2 TRIAL Imaging Working Group, Laura J. Esserman, Nola M. Hylton. FES-dedicated breast PET uptake in early-stage ER+ breast cancers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-02.