Expression of Epidermal Growth Factor Receptors Associated With Lack of Response to Endocrine Therapy in Recurrent Breast Cancer

Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI 182,780) in breast cancer cells

“…Rationales of this hypothesis are follows: (1) clinical studies have suggested that ER-positive breast cancers with a high expression level of EGFR or HER2 are frequently resistant to endocrine therapy and have a shorter survival time (Sainsbury et al, 1987;Nicholson et al, 1989;van Agthoven et al, 1992;Newby et al, 1995;Dowsett et al, 2001), (2) artificially increasing expression of EGFR or HER2 to high levels in ER-positive breast cancer cells leads to an antioestrogen-resistant phenotype (Benz et al, 1993;Houston et al, 1999), (3) a prolonged exposure of an antioestrogen to ERpositive breast cancer cells sometimes results in upregulation of EGFR or HER2 expression and an antioestrogen-resistant phenotype (Long et al, 1992;McClelland et al, 2001;Nicholson et al, 2002), (4) we and others have suggested that an anti-HER2 monoclonal antibody or inhibitor of HER2 signalling pathway enhances an antitumour effect of antioestrogens in ER-positive breast cancer cells with a moderate or high level of HER2 expression (Witters et al, 1997;Kunisue et al, 2000;Kurokawa et al, 2000). Actually, combination therapy with trastuzumab and an endocrine agent, the aromatase inhibitor anastrozole, has been tested in a clinical trial (Winer and Burstein, 2001).…”

“…It has been reported that EGFR/HER1 is expressed at high levels in at least 20% of breast cancers. This high expression has been suggested to correlate with a shorter survival time and resistance to endocrine therapy in patients with breast cancer (Sainsbury et al, 1987;Nicholson et al, 1989;Newby et al, 1995). In addition, a series of experimental and clinical findings have suggested that aberrant activation of tyrosine receptor kinases, such as EGFR/HER1 and HER2 pathways, play a causal role in the development of antioestrogen resistance in breast cancer (van Agthoven et al, 1992;Benz et al, 1993;Houston et al, 1999;Dowsett et al, 2001;Wakeling et al, 2001).…”

Functional identification of genes causing estrogen independence of human breast cancer cells

“…High expression of EGFR is associated with poor response to tamoxifen treatment [39]. Disruption of the AKT pathway by loss of PTEN, and mutation of PIK3CA and AKT1 is considered to contribute to the development and progression of breast cancer [40].…”

This month in APR

“…In the case of breast cancer, approximately 20% of all such cancers express high levels of EGFR, which has been implicated in shorter survival rate as well as increased resistance to hormonal therapy (Nicholson et al, 1989). Therefore, it is generally suggested that EGFR-targeted therapy may be an ideal adjuvant therapy for certain breast cancer patients.…”