Abstract
It is unknown whether the current dose of fulvestrant, an estrogen receptor (ER) antagonist, is sufficient for maximal ER downregulation in patients with metastatic breast cancer. We performed a feasibility study to assess ER availability before and during fulvestrant. Sixteen patients with ER-positive metastatic breast cancer underwent positron emission tomography/computed tomography (PET/CT) at baseline (scan 1), day 28 (scan 2), and day 84 (scan 3) to monitor tumor [(18)F]fluoroestradiol (FES) uptake. Incomplete reduction in ER availability was predefined as <75% decrease in median tumor FES uptake and a residual standardized uptake value (SUVmax) of ≥1.5. In total, 131 FES-positive lesions were identified (median SUVmax of 2.9; range, 1.7-6.5). The median change in patients during fulvestrant treatment was -85% at scan 2, but varied widely (-99% to +60%). Fulvestrant reduced tumor FES uptake incompletely at scan 2 in 6 (38%) of the 16 patients, which was associated with early progression. Serial imaging of tumor estrogen uptake by FES-PET can give insight into the dose needed for ER antagonists to completely abolish ER. FES-PET showed significant residual ER availability in tumors during fulvestrant therapy in 38% of patients, which was associated with early progression.
Highlights
Fulvestrant, a pure estrogen receptor (ER) antagonist, is used as treatment for advanced and metastatic ER-positive breast cancer
FES uptake at the earlier scan during aromatase inhibitor therapy was higher. If this scan was used as the baseline scan, FES uptake would have decreased by 26% during fulvestrant treatment, correctly identifying this patient as nonresponder. These results suggest that tamoxifen and its metabolites partly block FES uptake in the tumor, even after a 5-week drug-free period
When data adjusted for previous tamoxifen use were included, the positive predictive value increased to 89% and negative predictive value remained at 100%. This is the first serial PET imaging study evaluating the effects of fulvestrant 500 mg on FES uptake in patients with metastatic breast cancer
Summary
Fulvestrant, a pure estrogen receptor (ER) antagonist, is used as treatment for advanced and metastatic ER-positive breast cancer. Fulvestrant was shown to completely downregulate tumor ER expression and inhibit estrogen-mediated tumor growth [2]. Serial biopsy studies showed that ER expression is downregulated incompletely at the 250-mg dose [4]. A loading-dose regimen was explored more recently: 500 mg at day 1 and 250 mg at days 14 and 28 and every 4 weeks thereafter, as well as a high-dose regimen consisting of 500 mg at days 1, 14, and 28 and every 4 weeks thereafter. Because of a progression-free survival (PFS) gain in the highdose regimen from 5.5 to 6.5 months in a phase III trial, the high-dose regimen became the current standard
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