PMID- 25762475
OWN - NLM
STAT- MEDLINE
DCOM- 20151204
LR  - 20220408
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 150
IP  - 2
DP  - 2015 Apr
TI  - Revisiting the estrogen receptor pathway and its role in endocrine therapy for 
      postmenopausal women with estrogen receptor-positive metastatic breast cancer.
PG  - 231-42
LID - 10.1007/s10549-015-3316-4 [doi]
AB  - Endocrine therapy (ET) is the most commonly administered first-line systemic 
      therapy for estrogen receptor-positive (ER+) metastatic breast cancer (MBC). 
      Manipulation of hormone levels was one of the earliest ET approaches. However, 
      treatment modalities have since evolved with the growing understanding of 
      estrogen biosynthesis and ER biology. The current armamentarium of ET includes 
      selective estrogen receptor modulation, aromatase inhibition, and selective 
      estrogen receptor downregulation. However, intrinsic or acquired resistance to ET 
      is frequently observed. Significant strides have been made in recent years in our 
      understanding of the mechanisms of resistance to ET, and several targeted 
      approaches including inhibitors against the phosphatidylinositol 
      3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway and cyclin-dependent 
      kinase 4/6 (CDK4/6) have shown great promise. The mTOR inhibitor, everolimus, is 
      already in clinical use for the treatment of resistant ER+MBC. However, multiple 
      levels of evidence indicate that ER signaling remains as an important therapeutic 
      target even in the resistance setting, providing the rationale for sequencing 
      multiple lines and combinations of ET. In addition, recurrent mutations in 
      estrogen receptor 1 (ESR1), the gene that encodes the ER, have been identified in 
      the genomic studies of metastatic ER+ breast cancer. ESR1 mutations are an 
      important mechanism for acquired resistance, and effective ER targeting in this 
      setting is particularly important.
FAU - Nagaraj, Gayathri
AU  - Nagaraj G
AD  - Division of Medical Oncology & Hematology, Department of Medicine, Loma Linda 
      University, 11175 Campus Street, CSP 11015, Loma Linda, CA, USA, 
      gnagaraj@llu.edu.
FAU - Ma, Cynthia
AU  - Ma C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150312
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Receptors, Estrogen)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Hormonal/pharmacology/*therapeutic use
MH  - Aromatase Inhibitors/pharmacology/therapeutic use
MH  - Breast Neoplasms/drug therapy/*metabolism/pathology
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Neoplasm Metastasis
MH  - Postmenopause
MH  - Receptors, Estrogen/*metabolism
MH  - Signal Transduction
EDAT- 2015/03/13 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/03/13 06:00
PHST- 2014/10/28 00:00 [received]
PHST- 2015/02/19 00:00 [accepted]
PHST- 2015/03/13 06:00 [entrez]
PHST- 2015/03/13 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1007/s10549-015-3316-4 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2015 Apr;150(2):231-42. doi: 10.1007/s10549-015-3316-4. 
      Epub 2015 Mar 12.