Paoletti Costanza, Regan Meredith M, Niman Samuel M, Dolce Emily M, Darga Elizabeth P, Liu Minetta C, Marcom P Kelly, Hart Lowell L, Smith John W, Tedesco Karen L, Amir Eitan, Krop Ian E, DeMichele Angela M, Goodwin Pamela J, Block Margaret, Aung Kimberly, Brown Martha E, McCormack Robert T, Hayes Daniel F
Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
Currently at EISAI, Inc., Woodcliff Lake, NJ, USA.
NPJ Breast Cancer. 2021 Jun 11;7(1):77. doi: 10.1038/s41523-021-00281-1.
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）对转移性乳腺癌（MBC）具有预后价值。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），可能预测雌激素受体阳性MBC患者对内分泌治疗（ET）的耐药性。121例雌激素受体阳性/HER2阴性MBC患者在接受≥1线ET治疗后开始新的ET治疗，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及临床/影像学随访。无进展生存期（PFS）和快速进展（RP，在3个月时间点确定）为主要终点。使用对数秩检验和Fisher精确检验分析与临床结局的相关性。基线时，36%（38/107）的患者每7.5毫升全血（WB）中CTC≥5个。每7.5毫升WB中CTC≥5个与＜5个的患者相比，PFS显著更差（中位值3.3个月对5.9个月，P = 0.03）。1个月时CTC升高与更差的PFS相关（从1个月样本开始分别为1.9个月对5.0个月，P＜0.001）。71例（66%）、8例（8%）和28例（26%）患者分别观察到低、中、高CTC-ETI，中位PFS分别为6.9个月、8.5个月和2.8个月（P = 0.008）。高CTC和高CTC-ETI的患者比低CTC和低CTC-ETI的患者更频繁地经历RP（CTC：66%对41%；P = 0.03；CTC-ETI：79%对40%；P = 0.002）。总之，对于开始新ET治疗的雌激素受体阳性/HER2阴性MBC患者，CTC计数和CTC-ETI检测在基线和随访时具有预后价值。首次随访时的CTC可能识别出一组可以放弃ET治疗的雌激素受体阳性MBC患者，但CTC-ETI没有进一步的预测作用。
