Positron emission tomography of tumour [18F]fluoroestradiol uptake in patients with acquired hormone-resistant metastatic breast cancer prior to oestradiol therapy

PURPOSE: Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[(18)F]fluoro-17β-oestradiol ((18)F-FES) as potential marker to select breast cancer patients for oestradiol therapy. METHODS: Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent (18)F-FES-PET/CT imaging at baseline. Tumour (18)F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUVmax). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. RESULTS: (18)F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37%) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of (18)F-FES-PET for response to treatment were 60% (95% CI: 31-83%) and 80% (95% CI: 38-96%), respectively, using SUVmax >1.5. CONCLUSION: (18)F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy.