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Low-dose metronomic chemotherapy as an efficient treatment option in metastatic breast cancer-results of an exploratory case-control study.

低剂量节拍化疗作为转移性乳腺癌的有效治疗选择 -- 一项探索性病例对照研究的结果。

  • 影响因子:3.45
  • DOI:10.1007/s10549-020-05711-5
  • 作者列表:"Krajnak S","Schnatz C","Almstedt K","Brenner W","Haertner F","Heimes AS","Lebrecht A","Makris GM","Schwab R","Hasenburg A","Schmidt M","Battista MJ
  • 发表时间:2020-07-01
Abstract

PURPOSE:There is growing interest in low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case-control analysis, we compared the efficacy of LDMC and conventional chemotherapy (CCT) in MBC. METHODS:Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two controls who received CCT. Age, number of chemotherapy lines and metastatic sites as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate longer than 24 weeks (DCR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR) and subgroup analyses using the matching criteria. RESULTS:40 cases and 80 controls entered the study. 30.0% patients with LDMC and 22.5% patients with CCT showed DCR (p = 0.380). The median PFS was 12.0 weeks in both groups (p = 0.218) and the median DoR was 31.0 vs. 20.5 weeks (p = 0.383), respectively. Among younger patients, DCR was 40.0% in LDMC vs. 25.0% in the CCT group (p = 0.249). DCR was achieved in 33.3% vs. 26.2% non-heavily pretreated patients (p = 0.568) and in 36.0% vs. 18.0% patients without multiple metastases (p = 0.096), respectively. In the HR-positive group, 30.0% LDMC vs. 28.3% CCT patients showed DCR (p = 1.000). Among triple-negative patients, DCR was achieved in 30.0% LDMC and 5.0% CCT patients (p = 0.095). CONCLUSIONS:We demonstrated a similar efficacy of LDMC compared to CCT in the treatment of MBC. Thus, LDMC may be a valuable treatment option in selected MBC patients.

摘要

目的: 低剂量节拍化疗 (LDMC) 治疗转移性乳腺癌 (MBC) 的兴趣越来越大。在这项回顾性病例对照分析中,我们比较了 LDMC 和常规化疗 (CCT) 在 MBC 中的疗效。 方法: 每例接受口服环磷酰胺 (CTX) (每日 50 mg) 和甲氨蝶呤 (MTX) (隔日 2.5 mg) 的 LDMC 患者与接受 CCT 的 2 例对照。年龄、化疗线数和转移部位以及激素受体 (HR) 状态被认为是匹配标准。主要终点是疾病控制率超过 24 周 (DCR)。次要终点是无进展生存期 (PFS) 、缓解时间 (DoR) 和使用匹配标准的亚组分析。 结果: 40 例病例和 80 例对照进入研究。30.0% 例 LDMC 患者和 22.5% 例 CCT 患者显示 DCR (p = 0.380)。两组中位 PFS 分别为 12.0 周 (p = 0.218),中位 DoR 分别为 31.0 和 20.5 周 (p = 0.383)。在年轻患者中,DCR 在 LDMC 中为 40.0%,在 CCT 组中为 25.0% (p = 0.249)。DCR 分别在 33.3% vs. 26.2% 非重度预处理患者 (p = 0.568) 和 36.0% vs. 18.0% 无多发转移患者 (p = 0.096) 中实现。在 HR 阳性组中,30.0% 的 LDMC vs. 28.3% 的 CCT 患者显示 DCR (p = 1.000)。在三阴性患者中,30.0% LDMC 和 5.0% CCT 患者达到 DCR (p = 0.095)。 结论: 我们证明了 LDMC 与 CCT 治疗 MBC 的疗效相似。因此,在选定的 MBC 患者中,LDMC 可能是一个有价值的治疗选择。

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影响因子:2.87
发表时间:2020-01-31
来源期刊:Bioscience reports
DOI:10.1042/BSR20192546
作者列表:["Chen X","Theobard R","Zhang J","Dai X"]

METHODS::RAD50 is commonly depleted in basal-like breast cancer with concomitant absence of INPP4B and several tumor suppressors such as BRCA1 and TP53. Our previous study revealed that INPP4B and RAD50 interact and such an interaction is associated with breast cancer survival at the transcriptional, translational and genomic levels. In the present study, we explored single nucleotide polymorphisms (SNPs) of these two genes that have synergistic effects on breast cancer survival to decipher mechanisms driving their interactions at the genetic level. The Cox's proportional hazards model was used to test whether SNPs of these two genes are interactively associated with breast cancer survival, following expression quantitative trait loci (eQTL) analysis and functional investigations. Our study revealed two disease-associating blocks, each encompassing five and two non-linkage disequilibrium linked SNPs of INPP4B and RAD50, respectively. Concomitant presence of any rare homozygote from each disease-associating block is synergistically prognostic of poor breast cancer survival. Such synergy is mediated via bypassing pathways controlling cell proliferation and DNA damage repair, which are represented by INPP4B and RAD50. Our study provided genetic evidence of interactions between INPP4B and RAD50, and deepened our understandings on the orchestrated genetic machinery governing tumor progression.

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影响因子:3.29
发表时间:2020-01-31
来源期刊:BMC cancer
DOI:10.1186/s12885-020-6534-z
作者列表:["Soliman H","Shah V","Srkalovic G","Mahtani R","Levine E","Mavromatis B","Srinivasiah J","Kassar M","Gabordi R","Qamar R","Untch S","Kling HM","Treece T","Audeh W"]

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