内分泌治疗是雌激素受体阳性乳腺癌的主要治疗方法，雌激素受体表达水平可以预测内分泌治疗效果，但是通常需要对病灶进行有创伤的活检，然后在体外进行免疫组化分析。对于远处复发转移的晚期乳腺癌患者，确定全身雌激素受体表达水平非常重要，这些患者如果对内分泌治疗有效，那么可以避免化疗的毒性和不良反应，但是活检存在创伤性，难以多次或全身多处进行，只能检测病灶局部，无法反映全身雌激素受体水平，免疫组化显示雌激素受体阳性也不能准确预测内分泌治疗效果。
正电子发射计算机体层成像（PET/CT）结合PET和CT两种技术的优势，将人体代谢所必需的物质（例如葡萄糖、蛋白质、核酸、激素）标记能够发射正电子而半衰期很短的同位素（例如氟-18，原子核缺少1个中子，极不稳定，可发射出1个正电子而变成氧-18，半衰期仅109.771分钟）制成显像剂注入人体后，正电子遇到电子发生湮灭并释放出一对 γ光子，由探测器接收 γ光子，再经计算机重建出人体分层图像的成像，可同时获得病变部位和全身的功能代谢状况和精确解剖结构定位信息，并可以图像融合的方式显示结果。人体雌激素全部通过芳香化酶由雄激素转化而来，主要有雌酮、雌二醇、雌三醇，分别占10%～20%、10%～30%、60%～80%，虽然雌三醇最多，但是作用最弱，主要在怀孕期间发挥作用，而雌酮是绝经后女性体内雌激素的主要形式，雌二醇的作用大约是雌三醇的80倍，是绝经前未怀孕女性最重要的雌激素。将氟-18取代雌二醇第16α位的碳原子制成显像剂（18F-FES）用于PET/CT，可以准确反映病变部位和全身的雌激素受体表达水平。那么，18F-FES PET/CT能否取代活检，准确预测雌激素受体阳性晚期乳腺癌内分泌治疗长期效果？
2024年2月27日，欧洲肿瘤内科学会《肿瘤学年鉴》在线发表意大利东皮埃蒙特大学马乔里医院、热那亚大学加列拉医院和圣马蒂诺综合医院、罗马涅地区癌症中心、拉拉大学圣安娜费医院、帕尔马大学医院、法国居里研究中心雷内·胡格南医院、乔治-弗朗索瓦·勒克莱尔癌症中心、德国慕尼黑大学医院、西班牙巴塞罗那国际乳腺癌中心、马德里欧罗巴大学的ET-FES研究报告，探讨了18F-FES PET/CT对雌激素受体阳性HER2阴性晚期乳腺癌内分泌治疗长期效果的早期预测作用。
该国际多中心随机对照二期临床研究于2015年4月25日～2020年12月20日从4个国家7个中心入组晚期乳腺癌患者147例，治疗前进行18F-FES PET/CT检查：
标准化摄取值≥2的117例患者：给予单药内分泌治疗直至疾病进展
标准化摄取值<2的30例患者：按1∶1随机分为两组：A组（14例）单药内分泌治疗、B组（16例）化疗
该研究主要目的是比较18F-FES标准化摄取值<2患者一线内分泌治疗与化疗的长期效果。
结果，中位随访62.4个月后，104例患者（73.2%）疾病进展，53例患者（37.3%）死亡。
A组、B组、标准化摄取值≥2的患者相比：
中位无进展生存：12.4、23.0、18.0个月（95%置信区间：3.1～59.6、7.7～30.0、11.2～23.1，A组与B组风险比：0.71，95%置信区间：0.3～1.7）
中位总生存：28.2、52.8、未达中位（95%置信区间：14.2～未达、16.2～未达）
60个月总生存率：41.6%、42.0%、59.6%（95%置信区间：10.4～71.1%、14.0～68.2%、48.6～69.0%）
对于标准化摄取值≥2的患者，芳香化酶抑制剂与雌激素受体抑制剂（氟维司群或他莫昔芬）相比60个月总生存率72.6%比40.6%（P<0.005）。
Ann Oncol. 2024 Feb 27. IF: 50.5
Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): Pilot study with 18F-Fluoroestradiol (18F-FES) CT/PET.
Gennari A, Brain E, De Censi A, Nanni O, Wuerstlein R, Frassoldati A, Cortes J, Rossi V, Palleschi M, Alberini JL, Matteucci F, Piccardo A, Sacchetti G, Ilhan H, D'Avanzo F, Ruffilli B, Nardin S, Monti M, Puntoni M, Fontana V, Boni L, Harbeck N; ET-FES Collaborative Group.
University of Piemonte Orientale, Novara, Italy; Maggiore University Hospital, Novara, Italy; E.O. "Ospedali Galliera, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy; S. Anna University Hospital, Ferrara, Italy; University Hospital of Parma, Parma, Italy; Institut Curie - Hopital René Huguenin, Saint-Cloud, France; Centre Georges-Francois Leclerc, Dijon Cedex, France; LMU University Hospital, Munich, Germany; International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain; Universidad Europea de Madrid, Madrid, Spain.
HIGHLIGHTS
18F-FES PET/CT may be used as a predictive tool of efficacy of ET to assess overall endocrine sensitivity.
Endocrine sensitive patients (SUVmax ≥2) treated with single agent ET have a prolonged overall survival.
In endocrine sensitive patients PFS and OS related to the use of AI was significantly higher than ER directed agents.
18F-FES PET/CT can be used as a valid alternative to biopsy.
BACKGROUND: 18F-FES PET/CT is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the ET-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in ER+/HER2- metastatic breast cancer (MBC).
METHODS: Eligible patients underwent a 18F-FES PET/CT at baseline. Patients with SUV≥2 received single agent ET until PD; patients with SUV<2 were randomized to single agent ET (Arm A) or chemotherapy (CT) (Arm B). Primary objective was to compare the activity of first line ET versus CT in patients with 18F-FES SUV <2.
RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV≥2 and received ET; 30 pts with SUV<2 were randomized to ET or CT. After a median follow up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median PFS was 12.4 months (95%CI 3.1-59.6) in patients with SUV <2 randomised to Arm A versus 23.0 months (95%CI 7.7-30.0) in Arm B, (HR = 0.71, 95%CI 0.3 - 1.7); median PFS was 18.0 months (95%CI 11.2-23.1) in patients with SUV≥2 treated with ET. Median OS was 28.2 months (95%CI 14.2-NE) in patients with SUV <2 randomized to ET (Arm A) versus 52.8 months (95%CI 16.2-NE) in Arm B (CT). Median OS was not reached in patients with SUV≥2. 60-month OS rate was 41.6% (95%CI 10.4-71.1%) in Arm A, 42.0% (95%CI 14.0-68.2%) in Arm B and 59.6% (95%CI 48.6-69.0%) in patients with SUV≥2. In patients with SUV≥2, 60-months OS rate was 72.6% if treated with aromatase inhibitors versus 40.6% in case of fulvestrant or tamoxifen (p<0.005).
CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.
KEYWORDS: Endocrine sensitivity, Molecular Imaging, Randomized Clinical Trial, 18F-Fluoroestradiol PET/CT, Standardized Uptake Value (SUV)
DOI: 10.1016/j.annonc.2024.02.007
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