Dehdashti Farrokh, Mortimer Joanne E, Trinkaus Kathryn, Naughton Michael J, Ellis Matthew, Katzenellenbogen John A, Welch Michael J, Siegel Barry A
Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, St Louis, MO 63110, USA.
Breast Cancer Res Treat. 2009 Feb;113(3):509-17. doi: 10.1007/s10549-008-9953-0. Epub 2008 Mar 9.
To determine if response to endocrine therapy of breast cancer can be predicted by either a metabolic "flare reaction" detected by positron emission tomography (PET) with 2-[(18)F]-fluoro-2-deoxyglucose (FDG), induced by an estradiol challenge, or by estrogen-receptor (ER) status, determined by PET with the estrogen analog 16alpha-[(18)F]fluoroestradiol-17beta (FES).
Fifty-one post-menopausal women with advanced estrogen-receptor positive breast cancer were studied. Patients underwent FES-PET and FDG-PET at baseline and repeat FDG-PET after 30 mg estradiol. Tracer uptakes was measured as the standardized uptake value (SUV). Patients were subsequently treated with either an aromatase inhibitor or fulvestrant. A prospectively defined cut-off SUV >or= 2 for FES was considered positive for ER expression. A cutoff of >or=12% increase in SUV for FDG, determined by ROC analysis, represented metabolic flare. PET results were correlated with responsiveness to endocrine therapy.
Seventeen patients responded and 34 patients did not respond to endocrine therapy. Four responders and one non-responder had a clinical flare reaction, while only the responders demonstrated metabolic flare. After estradiol challenge, a significantly higher mean (+/-SD) percent change in SUV for FDG was noted in responders (20.9 +/- 24.2) compared with non-responders (-4.3 +/- 11.0, P < 0.0001). On FES-PET, a higher tumor SUV was noted in responders (3.5 +/- 2.5) compared with non-responders (2.1 +/- 1.8, P = 0.0049). There was significantly longer overall survival in patients with metabolic flare than in those without flare regardless of type of endocrine therapy (P = 0.0062).
Baseline tumor FES uptake and metabolic flare after an estradiol challenge are both predictive of responsiveness to endocrine therapy in ER+ breast cancer.
确定通过以下两种方法能否预测乳腺癌内分泌治疗的反应：一是由雌二醇激发试验诱发的、通过正电子发射断层扫描（PET）用2-[(18)F]-氟-2-脱氧葡萄糖（FDG）检测到的代谢“flare反应”；二是通过用雌激素类似物16α-[(18)F]氟雌二醇-17β（FES）进行PET检测确定的雌激素受体（ER）状态。
对51名绝经后晚期雌激素受体阳性乳腺癌患者进行研究。患者在基线时接受FES-PET和FDG-PET检查，并在注射30mg雌二醇后重复进行FDG-PET检查。示踪剂摄取以标准化摄取值（SUV）来衡量。患者随后接受芳香化酶抑制剂或氟维司群治疗。FES的SUV≥2的前瞻性定义切点被认为ER表达阳性。通过ROC分析确定，FDG的SUV增加≥12%代表代谢flare。PET结果与内分泌治疗反应性相关。
17名患者对内分泌治疗有反应，34名患者无反应。4名有反应者和1名无反应者出现临床flare反应，而只有有反应者表现出代谢flare。雌二醇激发试验后，有反应者的FDG的SUV平均（±标准差）变化百分比（20.9±24.2）显著高于无反应者（-4.3±11.0，P<0.0001）。在FES-PET上，有反应者的肿瘤SUV（3.5±2.5）高于无反应者（2.1±1.8，P=0.0049）。无论内分泌治疗类型如何，有代谢flare的患者的总生存期显著长于无flare的患者（P=0.0062）。
基线肿瘤FES摄取和雌二醇激发试验后的代谢flare均能预测ER+乳腺癌内分泌治疗的反应性。
