BACKGROUND Adding cyclin-dependent kinase (CDK) inhibitor to endocrine treatment improves outcome in œstrogen receptor (ER) positive metastatic breast cancer, but identifying the subset of patients who benefit is challenging. Response is potentially associated with ER expression heterogeneity. This is because, unlike the primary tumour in the breast that is localized to the organ, the metastatic breast cancer has spread and continues to spread to distant locations in the body such as bones, lungs, liver, axial skeleton, even to the central nervous system like the brain, wherefrom obtaining biopsies are not easy, and also, the metastasised tissues are heterogeneous. Positron emission tomography (PET) with 16α-[18F]fluoro-17β-œstradiol (FES), briefly referred to as FES-PET, allows whole-body ER assessment. We explored whether FES-PET heterogeneity and FES uptake were related to letrozole and palbociclib outcome, in patients with ER positive, metastatic breast cancer. PATIENTS AND METHODS Patients underwent a baseline FES-PET and 18F-fluorodeoxyglucose (FDG) PET, the FDG-PET served to help identify active sites of breast cancer with contrast-enhanced computed tomography (CT). FES-PET heterogeneity score (% FES positive lesions divided by all lesions on FDG-PET and/or CT) and FES uptake were related to outcome and 8-week FDG-PET response. Circulating tumour DNA (CtDNA) samples for ESR1 mutation analysis were collected at baseline. RESULTS In 30 patients with 864 metastatic lesions, baseline FES-PET heterogeneity was assessed. In 27 patients with 688 lesions, response was evaluated. Median time to progression (TTP) was 73 weeks (95% confidence interval [CI] 21 to ∞) in 7 patients with 100% FES positive disease, 27 weeks (14-49) in heterogeneous FES positive disease (20 patients), and 15 weeks (9 to ∞) without FES positivity (three patients; log-rank P = 0.30). Geometric mean FES uptake was 2.3 for metabolic progressive patients, 2.5 (Pvs progression = 0.82) for metabolic stable disease, and 3.3 (Pvs progression = 0.40) for metabolic response (Ptrend = 0.21). ESR1 mutations, found in 13/23 patients, were unrelated to FES uptake. CONCLUSION This exploratory study suggests that FES-PET heterogeneity may potentially identify the subset of ER positive, metastatic breast cancer patients who benefit from letrozole combined with CDK inhibition. CLINICAL TRIAL INFORMATION NCT02806050.

中文翻译：

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分子影像学识别出转移性乳腺癌患者，这些患者受益于内分泌治疗并结合细胞周期蛋白依赖性激酶抑制作用。

背景技术在内分泌治疗中添加细胞周期蛋白依赖性激酶（CDK）抑制剂可改善雌激素受体（ER）阳性转移性乳腺癌的预后，但确定受益的患者亚组具有挑战性。响应可能与ER表达异质性相关。这是因为，与定位在器官中的乳腺癌中的原发性肿瘤不同，转移性乳腺癌已经扩散并继续扩散到人体的远处，例如骨骼，肺，肝脏，轴向骨骼，甚至扩散到中枢神经像脑这样的系统，从那里获取活组织检查是不容易的，而且转移的组织是异质的。带有16α-[18F]氟-17β-雌二醇（FES）的正电子发射断层扫描（PET），简称为FES-PET，可用于全身ER评估。我们探讨了ER阳性，转移性乳腺癌患者中FES-PET异质性和FES摄取是否与来曲唑和palbociclib结果相关。患者和方法患者接受基线FES-PET和18F-氟脱氧葡萄糖（FDG）PET，FDG-PET通过对比增强计算机断层扫描（CT）有助于识别乳腺癌的活动部位。FES-PET异质性评分（％FES阳性病变除以FDG-PET和/或CT上的所有病变）和FES摄取与结局和8周FDG-PET反应有关。在基线时收集用于ESR1突变分析的循环肿瘤DNA（CtDNA）样品。结果在30例864个转移性病变患者中，评估了基线FES-PET异质性。在27个688个病灶的患者中，评估了反应。7例100％FES阳性疾病的患者的中位进展时间（TTP）为73周（95％置信区间[CI] 21至∞），异源FES阳性疾病的20名患者为27周（14-49），并且15周（9到∞）无FES阳性（3例；对数秩P = 0.30）。代谢进展患者的几何平均FES摄入量为2.3，代谢稳定疾病为2.5（Pvs进展= 0.82），代谢反应为3.3（Pvs进展= 0.40）（Ptrend = 0.21）。在13/23例患者中发现的ESR1突变与FES摄取无关。结论这项探索性研究表明，FES-PET异质性可能潜在地识别出从来曲唑联合CDK抑制中受益的ER阳性，转移性乳腺癌患者。临床试验信息NCT02806050。