Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial

The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway

“…These ligands bind to high-affinity EGFR in ER + cells, rendering the cells more dependent on the EGFR pathway and therefore more vulnerable to attack by gefitinib. This premise of dual action is further supported by the clinical trial (31) where ER + and EGFR + patients with breast cancer treated with gefitinib and anastrozole had a greater reduction from pretreatment values in the proliferation-related Ki67 labeling index than patients treated with gefitinib alone. Thus, HOXB7 overexpression in ER + breast cancer might have the potential to serve as a marker indicating anti-EGFR therapy.…”

Effects of gefitinib (Iressa) on mammary cancers: preventive studies with varied dosages, combinations with vorozole or targretin, and biomarker changes

“…Our laboratories have previously shown with a series of RXR agonists (19), as well as with a much more diverse series of agents (18), that compounds that strongly decreased proliferation and increased apoptosis were highly significant preventive agents and tended to be therapeutic in this mammary cancer model. In fact, in a neoadjuvant setting examining stage I/II tumors that were ER + and EGFR1 + , Polychronis et al (8) showed that Iressa significantly decreased proliferation and caused >50% partial or complete responses during a 12-week treatment as a monotherapy. This clinical study had three important implications: (a) the use of these nonspecific biomarkers may be useful in identifying agents that are effective in early-stage cancer therapy and/or prevention; (b) the percentage of partial and complete responses in this subset of patients was much higher than one would have expected based on results in patients with advanced cancers, where <5% responded to Iressa; and (c) it was anticipated that Iressa would be considerably less effective than an aromatase inhibitor, given the profound efficacy of aromatase inhibitors in ER + tumors.…”

“…Although EGFR inhibitors as monotherapies in metastatic breast cancer exhibit limited efficacy (6,7), treatment with these inhibitors during earlier periods of carcinogenesis may be more promising. For example, Polychronis et al (8) found that 30% of ER + mammary cancers responded to Iressa as a monotherapy in the neoadjuvant setting. Because the EGFR family (EGFR1/2) plays a significant role in many human breast cancers, we determined whether the small molecular inhibitor Iressa might be an effective preventive agent in the methylnitrosourea (MNU)-induced mammary cancer model.…”

Posttranslational Protein Modifications

“…With a wide range of investigational drugs that exploit essential PTM events commonly required by many tumors, combination therapy is being used with various other forms of treatment. These include the use of various PTM inhibitors with chemotherapeutic adjuvants such as taxanes, nucleoside analogs, and platinum agents (70 -72); radiation therapy (73); combination therapy with estrogen receptor antagonists (53); and finally combinations of drugs that inhibit different forms of PTM (74,75). In several cases prolongation of patient survival was found when these combination therapies were used.…”