Estrogen/EGF receptor interactions in breast cancer: rationale for new therapeutic combination strategies

In the therapy of estrogen receptor (ER) positive human mammary carcinomas, the treatment with the antiestrogen tamoxifen has been well established. However, the development of hormone resistance is an important factor in breast cancer progression against endocrine therapy. The presence of the receptor for EGF (EGFR) correlates with lack of response towards antiestrogen therapy. The EGFR is not only involved in tumor cell growth, survival signaling, cell migration, metastasis formation and angiogenesis, but also seems to confer reduced responses of tumor cells towards anti-hormones. Concomitant inhibition of both, the receptors for estrogen and EGF may be necessary to improve breast cancer therapy.