A phase 2 study of 16α-[18F]-fluoro-17β-estradiol positron emission tomography (FES-PET) as a marker of hormone sensitivity in metastatic breast cancer (MBC)

Abstract

Purpose: 16α-[(18)F]-fluoro-17β-estradiol positron emission tomography (FES-PET) quantifies estrogen receptor (ER) expression in tumors and may provide diagnostic benefit.

Procedures: Women with newly diagnosed metastatic breast cancer (MBC) from an ER-positive primary tumor were imaged before starting endocrine therapy. FES uptake was evaluated qualitatively and quantitatively, and associated with response and with ER expression.

Results: Nineteen patients underwent FES imaging. Fifteen had a biopsy of a metastasis and 15 were evaluable for response. Five patients had quantitatively low FES uptake, six had at least one site of qualitatively FES-negative disease. All patients with an ER-negative biopsy had both low uptake and at least one site of FES-negative disease. Of response-evaluable patients, 2/2 with low FES standard uptake value tumors had progressive disease within 6 months, as did 2/3 with qualitatively FES-negative tumors.

Conclusions: Low/absent FES uptake correlates with lack of ER expression. FES-positron emission tomography can help identify patients with endocrine resistant disease and safely measures ER in MBC.

Conflict of interest statement

Conflict of interest. None

Figures

Fig. 1

Imaging examples from two patients who underwent both FES and FDG scans prior to therapy. Left panel: Patient A (15-002) had mediastinal lesions appreciated by both FES and FDG. Right panel: Patient B (3-001) also had mediastinal disease clearly seen by FDG-PET, not visible on FES-PET. The core biopsy of a metastatic axillary lesion from Patient A showed ER+ breast cancer, while the needle biopsy of a vertebral lesion from Patient B showed ER- breast cancer.

Fig. 2

Alternative analysis methods for FES uptake. Panel a shows SUVmean for all lesions in the torso survey (black circles). Also displayed is the average for up to three lesions with highest FDG SUVmax (hollow squares). Panel b shows the FES/FDG ratio for all lesions in the torso survey, as well as the average for up to three lesions. For consistency, the horizontal axis for both panels is arranged by increasing average FES SUVmean (from the dynamic FOV). The different patient-level summaries follow different rank orders. For example, patient 6-018 (index #6 on the horizontal axis) had lesions with low FDG uptake, so the FES/FDG ratio was high relative to FES uptake.

Fig. 3

Association between quantitative FES uptake measures and ER expression in biopsy tissue. a The relationship between FES SUVmean (dynamic scan) mean and Allred scored levels of ER expression, for 13 lesions in 11 patients. The vertical dotted lines represent the division of a positive or negative Allred score. The horizontal dotted line depicts the previously established cutpoint of 1.5. Imaging and tissue assay classifications agree in all cases. b The relationship between FES SUVmean (torso scan) and ER expression, for 20 lesions in 13 patients. Imaging and tissue assay classifications appear to agree, although two lesions have low SUVmean scores in contrast to the Allred score of 8 for the biopsied material. Both discrepancies were from a single patient's axillary nodes with SUVmean of 1.1–1.2, in contrast to biopsy results (Allred 8 from a core biopsy, 11-019).

Fig. 4

Association between three patient-level quantitative measures of FES uptake and clinical response. a shows the distribution of response compared to FES SUVmean (dynamic scan). b The response distribution of FES SUVmean, for the three lesions in the torso sweep with highest FDG SUVmax. c The response distribution compared to the average FES/FDG ratio, for the three lesions in the torso sweep with lowest FES/FDG ratio.