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Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial
Breast Cancer Research ( IF 6.1 ) Pub Date : 2021-03-24 , DOI: 10.1186/s13058-021-01415-w
Francesca Galardi 1 , Francesca De Luca 1 , Chiara Biagioni 2 , Ilenia Migliaccio 1 , Giuseppe Curigliano 3, 4 , Alessandro M Minisini 5 , Martina Bonechi 1 , Erica Moretti 6 , Emanuela Risi 6 , Amelia McCartney 6, 7 , Matteo Benelli 2 , Dario Romagnoli 2 , Silvia Cappadona 6 , Stefano Gabellini 6 , Cristina Guarducci 1, 8 , Valerio Conti 9 , Laura Biganzoli 6 , Angelo Di Leo 6 , Luca Malorni 1, 6
Affiliation  

Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized patients with ABC to palbociclib alone or palbociclib plus the endocrine therapy received in the prior line of treatment. Moreover, we evaluated RB1 gene expression on CTCs and explored its prognostic role within the cTREnd subpopulation. Forty-six patients with ER-positive, HER2-negative ABC were analyzed. Blood samples were collected before starting palbociclib treatment (timepoint T0), after the first cycle of treatment (timepoint T1), and at disease progression (timepoint T2). CTCs were isolated and counted by CellSearch® System using the CellSearch™Epithelial Cell kit. Progression-free survival (PFS), clinical benefit (CB) during study treatment, and time to treatment failure (TTF) after study treatment were correlated with CTC counts. Samples with ≥ 5 CTCs were sorted by DEPArray system® (DA). RB1 and GAPDH gene expression levels were measured by ddPCR. All 46 patients were suitable for CTCs analysis. CTC count at T0 did not show significant prognostic value in terms of PFS and CB. Patients with at least one detectable CTC at T1 (n = 26) had a worse PFS than those with 0 CTCs (n = 16) (p = 0.02). At T1, patients with an increase of at least three CTCs showed reduced PFS compared to those with no increase (mPFS = 3 versus 9 months, (p = 0.004). Finally, patients with ≥ 5 CTCs at T2 (n = 6/23) who received chemotherapy as post-study treatment had a shorter TTF (p = 0.02). Gene expression data for RB1 were obtained from 19 patients. CTCs showed heterogeneous RB1 expression. Patients with detectable expression of RB1 at any timepoint showed better, but not statistically significant, outcomes than those with undetectable levels. CTC count seems to be a promising modality in monitoring palbociclib response. Moreover, CTC count at the time of progression could predict clinical outcome post-palbociclib. RB1 expression analysis on CTCs is feasible and may provide additional prognostic information. Results should be interpreted with caution given the small studied sample size.

中文翻译:

ER 阳性、HER2 阴性晚期乳腺癌患者的循环肿瘤细胞和 palbociclib 治疗:来自 TREnd 试验的转化子研究的结果

循环肿瘤细胞 (CTC) 可预测晚期乳腺癌 (ABC) 患者的预后。然而,没有关于它们在接受 palbociclib 治疗的患者中使用的数据。我们分析了 CTC 计数在参加 cTREnd 研究的患者中的预后作用,这是一项预先计划的 TREnd 转化子研究 (NCT02549430),该研究将 ABC 患者随机分配至单独使用 palbociclib 或 palbociclib 加内分泌治疗组治疗。此外,我们评估了 CTC 上的 RB1 基因表达并探讨了其在 cTREnd 亚群中的预后作用。对 46 名 ER 阳性、HER2 阴性 ABC 患者进行了分析。在开始 palbociclib 治疗前(时间点 T0)、第一个治疗周期后(时间点 T1)和疾病进展时(时间点 T2)收集血样。使用 CellSearch™ 上皮细胞试剂盒通过 CellSearch® 系统分离和计数 CTC。研究治疗期间的无进展生存期 (PFS)、临床获益 (CB) 和研究治疗后的治疗失败时间 (TTF) 与 CTC 计数相关。具有 ≥ 5 个 CTC 的样品通过 DEPArray 系统® (DA) 进行分类。通过ddPCR测量RB1和GAPDH基因表达水平。所有 46 名患者都适合进行 CTC 分析。T0 时的 CTC 计数在 PFS 和 CB 方面没有显示出显着的预后价值。在 T1 时具有至少一个可检测 CTC 的患者(n = 26)的 PFS 比具有 0 个 CTC 的患者(n = 16)更差(p = 0.02)。在 T1 时,与没有增加的患者相比,增加至少三个 CTC 的患者的 PFS 降低(mPFS = 3 与 9 个月,(p = 0.004)。最后,接受化疗作为研究后治疗的 T2 时具有 ≥ 5 个 CTC 的患者 (n = 6/23) 具有较短的 TTF (p = 0.02)。RB1 的基因表达数据来自 19 名患者。CTC 显示出异质的 RB1 表达。在任何时间点可检测到 RB1 表达的患者比那些无法检测到的患者表现出更好的结果,但没有统计学意义。CTC 计数似乎是监测 palbociclib 反应的一种有前途的方式。此外,进展时的 CTC 计数可以预测 palbociclib 后的临床结果。对 CTC 进行 RB1 表达分析是可行的,并可能提供额外的预后信息。鉴于研究样本量较小,应谨慎解释结果。CTC 显示出异质的 RB1 表达。在任何时间点可检测到 RB1 表达的患者比那些无法检测到的患者表现出更好的结果,但没有统计学意义。CTC 计数似乎是监测 palbociclib 反应的一种有前途的方式。此外,进展时的 CTC 计数可以预测 palbociclib 后的临床结果。对 CTC 进行 RB1 表达分析是可行的,并可能提供额外的预后信息。鉴于研究样本量较小,应谨慎解释结果。CTC 显示出异质的 RB1 表达。在任何时间点可检测到 RB1 表达的患者比那些无法检测到的患者表现出更好的结果,但没有统计学意义。CTC 计数似乎是监测 palbociclib 反应的一种有前途的方式。此外,进展时的 CTC 计数可以预测 palbociclib 后的临床结果。对 CTC 进行 RB1 表达分析是可行的,并可能提供额外的预后信息。鉴于研究样本量较小,应谨慎解释结果。进展时的 CTC 计数可以预测 palbociclib 后的临床结果。对 CTC 进行 RB1 表达分析是可行的,并可能提供额外的预后信息。鉴于研究样本量较小,应谨慎解释结果。进展时的 CTC 计数可以预测 palbociclib 后的临床结果。对 CTC 进行 RB1 表达分析是可行的,并可能提供额外的预后信息。鉴于研究样本量较小,应谨慎解释结果。
更新日期:2021-03-25
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