TY - JOUR
T1 - Combination therapy with aromatase inhibitors
T2 - The next era of breast cancer treatment?
AU - Leary, A.
AU - Dowsett, M.
PY - 2006/9/18
Y1 - 2006/9/18
N2 - Long-term endocrine therapy with either aromatase inhibitors (AIs) or tamoxifen may lead to endocrine resistance and disease progression. Recent years have seen advances in our understanding of the complex biological mechanisms associated with resistance. Growth factor signaling pathways appear to be upregulated in hormone-resistant tumours and interact with oestrogen-receptor (ER) signaling, which remains functional even after long-term endocrine deprivation. Signaling through the human epidermal and insulin-like growth-factor receptor (HER and IGFR, respectively) pathways may promote ligand-independent ER gene transcription and stimulate growth factor signaling. Therapeutic agents that inhibit these signal transduction pathways, when combined with AIs, may offer breast cancer patients new hope for more robust, longer-term remissions. Preliminary data from phase II studies of combination therapies are encouraging. There is a large programme of ongoing randomised, controlled trials, the results of which should pave the way for integrating combination therapies into clinical practice. To identify which patients will respond best to particular combinations of treatments, biomarkers and gene expression profiles are being investigated as predictors of sensitivity or resistance. In time, breast cancer treatment will become truly individualised because physicians will be able to match patients with a variety of disease phenotypes to optimal combination therapies.
AB - Long-term endocrine therapy with either aromatase inhibitors (AIs) or tamoxifen may lead to endocrine resistance and disease progression. Recent years have seen advances in our understanding of the complex biological mechanisms associated with resistance. Growth factor signaling pathways appear to be upregulated in hormone-resistant tumours and interact with oestrogen-receptor (ER) signaling, which remains functional even after long-term endocrine deprivation. Signaling through the human epidermal and insulin-like growth-factor receptor (HER and IGFR, respectively) pathways may promote ligand-independent ER gene transcription and stimulate growth factor signaling. Therapeutic agents that inhibit these signal transduction pathways, when combined with AIs, may offer breast cancer patients new hope for more robust, longer-term remissions. Preliminary data from phase II studies of combination therapies are encouraging. There is a large programme of ongoing randomised, controlled trials, the results of which should pave the way for integrating combination therapies into clinical practice. To identify which patients will respond best to particular combinations of treatments, biomarkers and gene expression profiles are being investigated as predictors of sensitivity or resistance. In time, breast cancer treatment will become truly individualised because physicians will be able to match patients with a variety of disease phenotypes to optimal combination therapies.
KW - Aromatase inhibitors
KW - Endocrine therapy
KW - Resistance
KW - Signal transduction inhibitors
KW - Targeted therapies
UR - http://www.scopus.com/inward/record.url?scp=33748578327&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6603316
DO - 10.1038/sj.bjc.6603316
M3 - Short survey
C2 - 16926831
AN - SCOPUS:33748578327
SN - 0007-0920
VL - 95
SP - 661
EP - 666
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 6
ER -