ANTIHORMONE DRUG RESISTANCE

The estrogen receptor (ER) has proved to be an excellent target for the treatment and prevention of breast cancer. Although the majority (80%) of breast cancer is ER positive, not all ER positive tumors respond to antihormone therapy. When an ER positive tumor does not respond at all to antihormone therapy it is described to have intrinsic resistance. This contrasts with acquired antihormone resistance where the tumor initially responds with regression but then cell populations expand that grow because of tamoxifen or despite estrogen deprivation. Based on laboratory studies using ER positive cell lines, the evolution of acquired antihormone resistance has been documented. Growth factor pathways expand and subvert the action of the ER at the genome. The new knowledge about molecular mechanisms of resistance has created new opportunities for combinations of antihormone therapies and inhibitors of growth factor pathways.