chapter  12
Individualization of Endocrine Therapy in Breast Cancer
ByAmelia B. Zelnak, Ruth M. O’Regan, and Clodia Osipo
Pages 17

Discovery of estrogen receptors (ER) was critical for the development of

endocrine therapy in breast cancer. Expression of ERa, the predominant isoform, in breast tumors of both premenopausal and postmenopausal women is a

highly predictive marker for response to antiestrogen treatment in women with

ERa-positive breast cancer. Today, endocrine therapies include the use of antiestrogens such as tamoxifen and aromatase inhibitors such as anastrozole,

exemestane, and letrozole. Tamoxifen, the first antiestrogen to be used for the

treatment of ERa-positive breast cancer, competitively blocks the actions of 17b-estradiol (E2), the female hormone that binds and activates ERa in tumors. In postmenopausal women, peripheral aromatization of androgens to estrogens

is the major source of plasma estrogen. Aromatase inhibitors inhibit this

reaction and consequently suppress the production of circulating estrogen in

postmenopausal women. Endocrine therapies are effective at reducing recur-

rence, increasing overall survival, and reducing contralateral breast cancer up

to 50%. However, about 50% of patients with ERa-positive breast cancer have

intrinsic resistance to antiestrogen therapy and therefore do not benefit. In

contrast to patients with intrinsically resistant tumors, there are patients who do

initially respond to antiestrogen therapy; however, most of these patients

develop acquired resistance during the treatment regimen. Therefore, the

current goal in breast cancer research is to elucidate the mechanisms of both

intrinsic and acquired resistance to tamoxifen and the aromatase inhibitors in

order to develop new therapeutic strategies to prevent and/or treat resistant

breast cancer.