Seventy five percent of all breast cancer (BC) patients express estrogen receptor
(ER) but a quarter to half of patients with ER positive BC relapse on ET (endocrine
therapy), tamoxifen, aromatase inhibitors (AIs), surgical castration, amongst other
treatment strategies. ER positive BC at relapse loses ER expression in 20 % of cases
and reduces quantitative ER expression most of the time. ER is not the only survival
pathway driving ER positive BC and escape pathways intrinsic or acquired are activated
during ET. This overview gives an account of ligand-independent ER activation, namely
by receptor networks cross talk, and by the various genomic factors and mechanisms
leading to ET response failure. Also the mechanisms of Her1 and Her2 inhibition resistance
are dealt within this overview, along with the therapeutic indications and limitations
of tyrosine kinase inhibitors, PARP inhibitors, PI3K/AKT/mTOR inhibitors, RAS/RAF/MEK/ERK/MAPK
inhibitors, and antiangiogenic drugs. In spite of the many advances in controlling
the division of BC cells and the progression of BC tumors these still remain the main
cause of death among women in age range of 20-50 years requiring even more efforts
in new therapeutic approaches besides the drugs within the scope of the overview.
