Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.

循环肿瘤细胞 (CTC) 是转移性乳腺癌 (MBC) 的预后因素。由 CTC-ER（雌激素受体）、BCL2、人表皮生长因子受体（HER2）和 Ki67 表达组成的 CTC-内分泌治疗指数（CTC-ETI）可能预测 ER 患者对内分泌治疗（ET）的耐药性-阳性 MBC。121 名 ER 阳性/HER2 阴性 MBC 在 ≥ 1 行 ET 后开始新 ET 的患者被纳入一项前瞻性、多机构临床试验。在基线和连续时间点进行 CTC-ETI 和临床/影像学随访。无进展生存期（PFS）和快速进展（RP；在 3 个月的时间点确定）是主要终点。与临床结果的关联使用对数秩和 Fisher 精确检验。在基线时，36% (38/107) 的患者有≥5 CTC/7.5 ml 全血 (WB)。P  = 0.03）。1 个月时升高的 CTC 与更差的 PFS 相关（1 个月样本的 1.9 个月与 5.0 个月，P  < 0.001）。在 71 (66%)、8 (8%) 和 28 (26%) 名患者中观察到低、中和高 CTC-ETI，中位 PFS 分别为 6.9、8.5 和 2.8 个月（ P = 0.008  ） . 高 vs. 低 CTC 和 CTC-ETI 患者经历 RP 的频率更高（CTC：66% vs. 41%；P  = 0.03；CTC-ETI：79% vs. 40%；P  = 0.002）。总之，CTC 计数和 CTC-ETI 检测可预测开始新 ET 的 ER 阳性/HER2 阴性 MBC 患者的基线和随访结果。第一次随访时的 CTC 可能会确定一组 ER 阳性 MBC 患者可以放弃 ET，但 CTC-ETI 没有进一步的贡献。