We previously reported the identification of the breast cancer anti-estrogen resistance 1 gene (BCAR1)  whose overexpression confers resistance against antiestrogen
drugs to an estrogen-dependent human breast cancer cell line (1).
We have identified BCAR1/p130Cas in a functional screen for proliferation of human breast cancer cells resistant to an antiestrogen
drug and provided evidence that high concentrations of BCAR1 protein in primary breast tumors are associated with poor prognosis (2,14).
2] was not significantly inhibited by antiestrogen
treatment (Figure 3B).
The US Food and Drug Administration (FDA) approved FASLODEX in 2002 for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen
therapy, such as tamoxifen.
Two nonsteroidal aromatase inhibitors, anastrozole and letrozole, are approved in the United States as first- or second-line treatment of hormone receptor-positive metastatic breast cancer, and one steroidal aromatase inactivator, exemestane, is approved for hormone therapy for women with metastatic breast cancer after disease progression or after antiestrogen
1995) so they may exert estrogen and antiestrogen
effects in organisms.
Results with Herceptin are of interest because they provide a new therapeutic option for some patients in whom antiestrogen
therapy (tamoxifen and raloxifen) is not effective (8,28).
TABLE 35 GLOBAL SALES OF ANTIESTROGEN
AND SELECTIVE ESTROGEN RECPTOR MODULATORS, THROUGH 2013 ($MILLIONS)
2] as a "positive" control, with its nonmonotonic and nonhormetic dose-response curve in comparison with BPA (which has a presumably monotonic response curve), as well as the use of an antiestrogen
(tamoxifen), is inappropriate.
In addition, it is indicated for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen
Numerous studies have shown that the antiestrogen
agent tamoxifen not only induces remission in advanced breast cancer but also prolongs relapse-free as well as overall survival rates when administered to breast cancer patients in the adjuvant setting (3).
In this study, patients with hormone receptor expressing advanced breast therapy whose disease had progressed on an antiestrogen
therapy are being randomized to treatment with either IMC-A12 as a single agent or IMC-A12 in combination with same dose and schedule of the last antiestrogen
therapy to which their disease became refractory.
Tamoxifen was not disqualified as an antiestrogen
because it elicited a binding higher than that of BPA.
Femara, a leading, once-a-day oral aromatase inhibitor, is also indicated for first-line treatment of postmenopausal women with hormone receptor- positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen
This observation is cause for concern in that giving tamoxifen may select for populations of breast cells that are antiestrogen