Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Lancet Oncol. 2019 Apr;20(4):546-555. doi: 10.1016/S1470-2045(18)30936-7. Epub 2019 Mar 4.
A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[F]fluoro-17β-oestradiol (F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer.
We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of F-FES, with dosing primarily determined by radiation dosimetry analysis. F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569.
Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded.
The high negative percent agreement between F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include F-FES PET-CT when retesting oestrogen receptor status is not feasible.
Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.
建议对患有乳腺癌的患者进行首次复发或转移性疾病的活检，以重新评估雌激素受体状态，并选择适当的治疗方法。但是，根据病变位置和活检相关风险，重新进行雌激素受体状态的活检并不总是可行的，在这些情况下，临床医生会根据原发性肿瘤的雌激素受体状态继续为患者治疗。因此，这些患者可能会接受不太理想的治疗。我们评估了 16α-[F]氟-17β-雌二醇（F-FES）PET-CT 重新评估复发性或转移性乳腺癌患者雌激素受体状态的诊断准确性和安全性。
我们在韩国首尔的 Asan 医疗中心进行了一项前瞻性队列研究。符合条件的患者患有乳腺癌，在初次就诊时出现复发或转移，年龄在 19 岁及以上，且东部合作肿瘤学组表现状态为 0-2。主要目的是展示 F-FES PET-CT 定性解读与雌激素受体表达免疫组织化学检测结果之间的一致性，后者是非参考标准检测。在静脉注射 111-222MBq 的 F-FES 后，进行全身 F-FES PET-CT 成像，剂量主要根据辐射剂量分析确定。将背景强度以上的 F-FES 摄取解读为阳性。在所有接受 F-FES 治疗且 PET-CT 图像可用的经组织学证实的复发性或转移性乳腺癌患者中进行疗效评估（意向诊断分析），并在所有接受 F-FES 治疗的患者中进行安全性评估。本研究在 ClinicalTrials.gov 注册，编号为 NCT01986569。
2013 年 11 月 27 日至 2016 年 11 月 10 日期间，共纳入 93 例患者。在纳入的 85 例疗效分析患者中，47 例（55%）为雌激素受体阳性，38 例（45%）为雌激素受体阴性。F-FES PET-CT 结果与雌激素受体状态免疫组织化学检测之间的阳性状态百分比一致性为 76.6%（95%CI 62.0-87.7），阴性状态百分比一致性为 100.0%（90.8-100.0）。雌激素受体阳性且 F-FES PET-CT 结果阳性的患者孕激素受体表达明显高于雌激素受体阳性且 F-FES PET-CT 结果阴性的患者（34 例患者中有 23 例[68%] vs 11 例患者中有 0 例[0%]；p<0.0001）。最常见的不良事件是 90 例注射 F-FES 的患者中有 10%（9 例）出现程序性疼痛。除了 1 例（1%）患者出现注射部位疼痛外，没有与研究药物相关的其他不良事件。未记录严重不良事件。
在本队列中，F-FES PET-CT 与雌激素受体状态免疫组织化学检测之间的高阴性百分比一致性表明，复发性或转移性雌激素受体阳性乳腺癌病变中 F-FES 的阳性摄取可能是该环境中雌激素受体检测的替代方法。在无法重新进行雌激素受体状态检测时，应包括 F-FES PET-CT 进行分期评估。
韩国卫生福利部 Asan 生命科学研究所。
