BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, representing 15% of all invasive breast cancers. Most ILC tumors are estrogen receptor-positive (ER+) and may respond to endocrine therapy. However, tumor biologic factors such as ER functionality, cell proliferation, and molecular traits may influence endocrine treatment response and long-term recurrence risk, thus necessitating a comprehensive approach to characterize the primary breast tumor. [18F]fluoroestradiol (FES) is a radiotracer developed for positron emission tomography (PET) imaging of ER status. For this work, we studied the utility of imaging FES uptake in early-stage primary ER+ ILC lesions, using high-resolution dedicated breast PET (dbPET) to assess the relationship between FES uptake and tumor characteristics. METHODS: With institutional review board approval, patients with biopsy-proven ER+/HER2- ILC were prospectively imaged using dbPET with 5 mCi of FES before treatment. FES uptake (SUVmax, SUVmean, and SUVpeak), tumor uptake volume (TUV), and background parenchymal uptake (BPU) values 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 grade, Ki67 cell proliferation index, and ER expression were obtained from core biopsies before treatment. Ki67 was dichotomized to low and high using a 20% cutoff1. Tumor size (longest diameter) was measured by magnetic resonance imaging (MRI). Spearman rank correlation was used to assess the relationship between FES uptake and tumor size. Differences between FES uptake at high and low Ki67 were compared using a Wilcoxon rank-sum test. RESULTS: 13 treatment-naïve ILC patients aged 32-82 years were included in this analysis (Table 1). Despite all lesions exhibiting strongly positive ER expression >90% by immunohistochemistry (IHC), we observed varying FES avidity with 9 FES avid and 4 FES non-avid ILC lesions. SUVmax, TUV, and TBR had substantial median differences between Ki67 high and low lesions (5.9, 4.3, and 9.6, respectively), but the difference did not achieve statistical significance. FES tumor uptake also correlated with tumor size, with the highest correlation observed for SUVpeak (ρ = 0.71 (95% CI: 0.22, 0.91), p=0.010) (Table 2). CONCLUSION: We found that not all highly ER expressing ILC by IHC were FES-avid. As FES-dbPET captures information from the entire tumor, it provides a more comprehensive assessment of functional ER status than IHC of a limited tumor sample. FES uptake in ILC also relates to tumor size and Ki67. 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. 1. Acs, B. et al. Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy. Diagn Pathol12, 20, doi:10.1186/s13000-017-0608-5 (2017).

Patient and tumor characteristics
CharacteristicsNumber of patients (Total N=13)
Age (median (range)) 56.0 (32-80) 
Pre-menopausal 
Post-menopausal 10 
  
MRI tumor size (median (interquartile range) 4.1 (2.4-6.8) 
Tumor grade  
  
Ki67 12 
Low/High 3/9 
  
FES 13 
Avid/Non-avid 9/4 
Patient and tumor characteristics
CharacteristicsNumber of patients (Total N=13)
Age (median (range)) 56.0 (32-80) 
Pre-menopausal 
Post-menopausal 10 
  
MRI tumor size (median (interquartile range) 4.1 (2.4-6.8) 
Tumor grade  
  
Ki67 12 
Low/High 3/9 
  
FES 13 
Avid/Non-avid 9/4 

Summary of FES uptake values and correlation coefficients.
FES avidity (N=13)Ki67 (N=12)MRI tumor size (N=12)
 Avid vs Non-avid  High vs Low  Spearman rank correlation  
 Median Difference (95% CI) P-value Median Difference (95% CI) P-value Spearman ρ (95% CI) P-value 
SUVmax 8.68 (2.86, 12) 0.007 5.9 (-19.5, 11.6) 0.14 0.67 (0.16, 0.9) 0.017 
SUVmean 2.56 (1.43, 4.86) 0.007 1.34 (-4.14, 3.1) 0.20 0.6 (0.042, 0.87) 0.039 
SUVpeak 2.86 (1.14, 4.59) 0.011 2.15 (-14.4, 3.72) 0.19 0.71 (0.22, 0.91) 0.01 
BPU -0.31 (-1.89, 1.02) 0.82 -0.73 (-2.34, 0.28) 0.096 0.01 (-0.57, 0.58) 0.98 
TUV (cm35.45 (1.04, 10) 0.01 4.3 (-185, 10) 0.19 0.70 (0.21, 0.91) 0.011 
TBR 3.61 (2.2, 13) 0.007 9.57 (-19.6, 12.4) 0.064 0.66 (0.13, 0.89) 0.02 
Summary of FES uptake values and correlation coefficients.
FES avidity (N=13)Ki67 (N=12)MRI tumor size (N=12)
 Avid vs Non-avid  High vs Low  Spearman rank correlation  
 Median Difference (95% CI) P-value Median Difference (95% CI) P-value Spearman ρ (95% CI) P-value 
SUVmax 8.68 (2.86, 12) 0.007 5.9 (-19.5, 11.6) 0.14 0.67 (0.16, 0.9) 0.017 
SUVmean 2.56 (1.43, 4.86) 0.007 1.34 (-4.14, 3.1) 0.20 0.6 (0.042, 0.87) 0.039 
SUVpeak 2.86 (1.14, 4.59) 0.011 2.15 (-14.4, 3.72) 0.19 0.71 (0.22, 0.91) 0.01 
BPU -0.31 (-1.89, 1.02) 0.82 -0.73 (-2.34, 0.28) 0.096 0.01 (-0.57, 0.58) 0.98 
TUV (cm35.45 (1.04, 10) 0.01 4.3 (-185, 10) 0.19 0.70 (0.21, 0.91) 0.011 
TBR 3.61 (2.2, 13) 0.007 9.57 (-19.6, 12.4) 0.064 0.66 (0.13, 0.89) 0.02 

Citation Format: Ella F Jones, Deep K Hathi, Natalia Konovalova, Julissa Molina-Vega, David C Newitt, Courtney Lawhn-Heath, Kimberly M Ray, Bonnie N Joe, Diane Heditsian, Susie Brain, I-SPY 2 TRIAL Imaging Working Group, I-SPY 2 TRIAL Consortium, A. Jo Chien, Laura J Esserman, Nola M Hylton, Rita A Mukhtar. Initial experience of FES-dedicated breast PET imaging of early-stage ER+ invasive lobular carcinoma [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 P3-02-01.