Abstract
About 75% of all breast cancers are estrogen receptor (ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. Anti-estrogens (such as tamoxifen and fulvestrant) and aromatase inhibitors (such as anastrozole, letrozole, and exemestane) can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of patients progress during endocrine therapy (acquired resistance) and a proportion of patients may fail to respond to initial therapy (de novo resistance). Endocrine resistance is therefore of clinical concern and there is great interest in strategies that delay or circumvent it. A deeper knowledge of the molecular mechanisms that drive endocrine resistance has recently led to development of new strategies that have the promise to effectively overcome it. Many resistance mechanisms have been described, and the crosstalk between ER and growth factor receptor signaling pathways seems to represent one of the most relevant. Compounds that are able to inhibit key elements of these pathways and restore endocrine sensitivity have been studied and more are currently under development. The aim of this review is to summarize the molecular pathophysiology of endocrine resistance in breast cancer and its impact on current clinical management.
| Original language | English |
|---|---|
| Pages (from-to) | 990-1001 |
| Number of pages | 12 |
| Journal | World Journal of Clinical Oncology |
| Volume | 5 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Dec 10 2014 |
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Keywords
- Endocrine resistance
- Estrogen receptor
- Everolimus
- Mammalian target of rapamycin
- PI3K inhibitors
ASJC Scopus subject areas
- Oncology
Cite this
Overcoming endocrine resistance in metastatic breast cancer : Current evidence and future directions. / Milani, Andrea; Geuna, Elena; Mittica, Gloria; Valabrega, Giorgio.
In: World Journal of Clinical Oncology, Vol. 5, No. 5, 10.12.2014, p. 990-1001.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overcoming endocrine resistance in metastatic breast cancer
T2 - Current evidence and future directions
AU - Milani, Andrea
AU - Geuna, Elena
AU - Mittica, Gloria
AU - Valabrega, Giorgio
PY - 2014/12/10
Y1 - 2014/12/10
N2 - About 75% of all breast cancers are estrogen receptor (ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. Anti-estrogens (such as tamoxifen and fulvestrant) and aromatase inhibitors (such as anastrozole, letrozole, and exemestane) can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of patients progress during endocrine therapy (acquired resistance) and a proportion of patients may fail to respond to initial therapy (de novo resistance). Endocrine resistance is therefore of clinical concern and there is great interest in strategies that delay or circumvent it. A deeper knowledge of the molecular mechanisms that drive endocrine resistance has recently led to development of new strategies that have the promise to effectively overcome it. Many resistance mechanisms have been described, and the crosstalk between ER and growth factor receptor signaling pathways seems to represent one of the most relevant. Compounds that are able to inhibit key elements of these pathways and restore endocrine sensitivity have been studied and more are currently under development. The aim of this review is to summarize the molecular pathophysiology of endocrine resistance in breast cancer and its impact on current clinical management.
AB - About 75% of all breast cancers are estrogen receptor (ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. Anti-estrogens (such as tamoxifen and fulvestrant) and aromatase inhibitors (such as anastrozole, letrozole, and exemestane) can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of patients progress during endocrine therapy (acquired resistance) and a proportion of patients may fail to respond to initial therapy (de novo resistance). Endocrine resistance is therefore of clinical concern and there is great interest in strategies that delay or circumvent it. A deeper knowledge of the molecular mechanisms that drive endocrine resistance has recently led to development of new strategies that have the promise to effectively overcome it. Many resistance mechanisms have been described, and the crosstalk between ER and growth factor receptor signaling pathways seems to represent one of the most relevant. Compounds that are able to inhibit key elements of these pathways and restore endocrine sensitivity have been studied and more are currently under development. The aim of this review is to summarize the molecular pathophysiology of endocrine resistance in breast cancer and its impact on current clinical management.
KW - Endocrine resistance
KW - Estrogen receptor
KW - Everolimus
KW - Mammalian target of rapamycin
KW - PI3K inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84938076531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938076531&partnerID=8YFLogxK
U2 - 10.5306/wjco.v5.i5.990
DO - 10.5306/wjco.v5.i5.990
M3 - Article
AN - SCOPUS:84938076531
VL - 5
SP - 990
EP - 1001
JO - World Journal of Clinical Oncology
JF - World Journal of Clinical Oncology
SN - 2218-4333
IS - 5
ER -