PMID- 25419366
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141124
LR  - 20220310
IS  - 1940-5901 (Print)
IS  - 1940-5901 (Electronic)
IS  - 1940-5901 (Linking)
VI  - 7
IP  - 10
DP  - 2014
TI  - Mammalian target of rapamycin (mTOR) inhibitors and combined chemotherapy in 
      breast cancer: a meta-analysis of randomized controlled trials.
PG  - 3333-43
AB  - The mammalian target of rapamycin (mTOR) inhibitor, in combination with other 
      chemotherapeutic drugs, has been used for treatment of breast cancer that 
      develops resistance to endocrine therapy. However, the efficacy and safety need 
      further evaluation. Here, we report a meta-analysis of randomized controlled 
      trials (RCT) in breast cancer patients undergoing chemotherapy using steroid 
      (exemestane) or nonsteroid (letrozole) aromatase inhibitors with or without mTOR 
      inhibitors (everolimus). The overall response rate (ORR), progression-free 
      survival (PFS), clinical benefi;t rate with 95% confidence interval (CI), and the 
      major toxicities/adverse effects were analyzed. Data were extracted from twelve 
      studies that meet the selection criteria. Among these, six studies that enrolled 
      3693 women received treatment of everolimus plus exemestane, or placebo with 
      exemestane. The results showed that everolimus plus exemestane significantly 
      increased the ORR relative risk (relative risk = 9.18, 95% CI = 5.21-16.15), PFS 
      hazard ratio (hazard ratio = 0.44, 95% CI = 0.41-0.48), and clinical benefi;t 
      rate (relative risk = 1.92, 95% CI 1.69-2.17) compared to placebo control, while 
      the risks of stomatitis, rash, hyperglycemia, diarrhea, fatigue, anorexia and 
      pneumonitis also increased. Three studies that enrolled 715 women who received 
      everolimus as neoadjuvant therapy were analyzed. Compared to chemotherapy with 
      placebo, chemotherapy plus everolimus did not increase the ORR relative risk 
      (relative risk = 0.90, 95% CI = 0.77-1.05). Meanwhile, two other studies that 
      enrolled 2104 women examined the efficacy of temsirolimus (or placebo control) 
      plus letrozole. The results indicated that emsirolimus plus letrozole did not 
      increase the ORR relative risk and clinical benefi;t rate (p > 0.05). Together, 
      these data suggest that the combined mTOR inhibitor (everolimus) plus endocrine 
      therapy (exemestane) is superior to endocrine therapy alone. As a neoadjuvant, 
      everolimus did not increase the ORR, while temsirolimus plus letrozole treatment 
      has limited effect on the ORR and the CBR of breast cancer patients.
FAU - Qiao, Longwei
AU  - Qiao L
AD  - Department of Hematology and Hematological Laboratory Science, School of Medical 
      Science and Laboratory Medicine, Jiangsu University Zhenjiang 212013, China.
FAU - Liang, Yuting
AU  - Liang Y
AD  - Department of Hematology and Hematological Laboratory Science, School of Medical 
      Science and Laboratory Medicine, Jiangsu University Zhenjiang 212013, China.
FAU - Mira, Ranim R
AU  - Mira RR
AD  - Department of Anatomy and Cell Biology, Rush University Medical Center Chicago, 
      IL 60612, USA.
FAU - Lu, Yaojuan
AU  - Lu Y
AD  - Department of Hematology and Hematological Laboratory Science, School of Medical 
      Science and Laboratory Medicine, Jiangsu University Zhenjiang 212013, China ; 
      Department of Anatomy and Cell Biology, Rush University Medical Center Chicago, 
      IL 60612, USA.
FAU - Gu, Junxia
AU  - Gu J
AD  - Department of Hematology and Hematological Laboratory Science, School of Medical 
      Science and Laboratory Medicine, Jiangsu University Zhenjiang 212013, China.
FAU - Zheng, Qiping
AU  - Zheng Q
AD  - Department of Hematology and Hematological Laboratory Science, School of Medical 
      Science and Laboratory Medicine, Jiangsu University Zhenjiang 212013, China ; 
      Department of Anatomy and Cell Biology, Rush University Medical Center Chicago, 
      IL 60612, USA.
LA  - eng
PT  - Journal Article
DEP - 20141015
PL  - United States
TA  - Int J Clin Exp Med
JT  - International journal of clinical and experimental medicine
JID - 101471010
PMC - PMC4238547
OTO - NOTNLM
OT  - aromatase inhibitors
OT  - breast cancer
OT  - chemotherapy
OT  - mTOR inhibitors
OT  - meta-analysis
EDAT- 2014/11/25 06:00
MHDA- 2014/11/25 06:01
PMCR- 2014/10/15
CRDT- 2014/11/25 06:00
PHST- 2014/08/17 00:00 [received]
PHST- 2014/09/21 00:00 [accepted]
PHST- 2014/11/25 06:00 [entrez]
PHST- 2014/11/25 06:00 [pubmed]
PHST- 2014/11/25 06:01 [medline]
PHST- 2014/10/15 00:00 [pmc-release]
PST - epublish
SO  - Int J Clin Exp Med. 2014 Oct 15;7(10):3333-43. eCollection 2014.