# Uptake Patterns of [18F]Fluoroestradiol PET/MRI in Benign Breast Lesions and Molecular Breast Cancer Subtypes

## TL;DR

This study examines how a PET/MRI imaging technique detects estrogen receptor activity in breast lesions, showing that it's effective for larger ER-positive tumors but less reliable for smaller ones or benign lesions.

## Contribution

The study provides new insights into the variability of 18F-FES uptake in benign breast lesions and its correlation with tumor size and ER status.

## Key findings

- Benign and malignant breast lesions < 10 mm showed low 18F-FES uptake.
- ER-positive tumors ≥ 10 mm had significantly higher tracer uptake compared to ER-negative tumors.
- 18F-FES uptake patterns were consistent across molecular and histologic breast cancer subtypes.

## Abstract

Hormone receptor status, in particular estrogen receptor (ER) status, plays a pivotal role in therapeutic decision-making in breast cancer. Positron emission tomography (PET) using a radiolabeled estrogen analog [18F]Fluoroestradiol (18F-FES) enables noninvasive, whole-body assessment of ER expression in vivo. In this retrospective analysis, we systematically evaluated imaging characteristics of breast lesions on ER-targeted PET/MRI to elucidate patterns of tracer uptake in benign lesions and across molecular breast cancer subtypes. All small breast lesions < 10 mm exhibited low 18F-FES uptake. Notably, a subset of benign lesions demonstrated tracer uptake overlapping with ER-positive malignancies, highlighting a potential diagnostic pitfall. ER-positive tumors ≥ 10 mm were characterized by high tracer uptake, whereas ER-negative tumors of comparable size consistently showed low uptake values. Overall, 18F-FES uptake patterns were concordant across molecular and histologic breast cancer subtypes. These findings provide clinically relevant insights that may enhance the interpretation of ER-targeted breast imaging and support its integration into clinical practice.

Background/Objectives: Estrogen receptor (ER) expression is a key biomarker in breast cancer (BC) and guides endocrine therapy selection. Estrogen receptor-targeted imaging with 16ɑ-[18F]-fluoro-17β-estradiol (18F-FES) PET is recommended in several clinical guidelines for noninvasive assessment of ER status. In clinical practice, 18F-FES PET may also identify ER-negative malignancies or benign breast lesions with variable uptake patterns. This study aimed to systematically characterize 18F-FES PET/MRI uptake patterns in benign breast lesions and across breast cancer subtypes defined by receptor status, histology, and molecular phenotype. Methods: This retrospective single-center study included 41 women with 50 breast lesions who underwent simultaneous 18F-FES PET/MRI prior to any treatment. Histopathology or long-term follow-up served as the standard of reference. Maximum and mean standardized uptake values (SUVmax and SUVmean) were derived using MRI-based lesion delineation. Results: Both benign and malignant breast lesions measuring < 10 mm demonstrated low 18F-FES uptake (SUVmax < 1.00). 18F-FES uptake among benign breast lesions was variable, with SUVmax ranging from 0.44 to 1.57. In contrast, ER-positive lesions ≥ 10 mm exhibited substantially higher 18F-FES uptake (median SUVmax 2.76; range 1.23–9.74) compared with ER-negative tumors of similar size (SUVmax 0.30–0.94). 18F-FES uptake was consistent across histologic BC subtypes and did not differ significantly among ER-positive molecular subtypes. No significant associations were observed with HER2 status or tumor grade. Conclusions: Awareness of the heterogeneous 18F-FES uptake patterns in benign breast lesions, as well as the limited sensitivity for detecting ER-positive tumors < 10 mm, is essential for accurate image interpretation. 18F-FES PET/MRI enables reliable assessment of ER expression in BC lesions ≥ 10 mm, with uptake patterns remaining consistent across molecular and histologic subtypes.