title: Towards a molecular basis for tamoxifen resistance in breast cancer.
abstract: Breast cancer patients who acquire tamoxifen resistance may respond to second-line hormonal therapy or progress to true endocrine resistance. The biological basis for these processes are poorly understood. Following successful therapy with tamoxifen there is little evidence at relapse for change in either the host endocrine environment or drug metabolic profile to account for the development of acquired resistance. Many tamoxifen resistant tumours still retain a structurally and functionally normal oestrogen receptor (ER) and yet will grow independent of oestrogen. The oestrogen-regulated molecular events which normally govern the growth of hormone-sensitive breast cancer involve a complex autocrine and paracrine interaction between several peptide growth factors (including TGF alpha, IGF-1 and TGF beta), their receptors and signal transduction pathways. Evidence now exists that constitutive activity of many of these mediators of the mitogenic signal can bypass the cell's dependence on oestrogen and provide a mechanism for hormone-independent growth. Research into these molecular mechanisms may result in a better understanding of how to overcome the clinical problem of tamoxifen resistance.
authors.affiliation: Department of Academic Biochemistry, Royal Marsden Hospital, London, U.K.
authors.forename: S R
authors.initials: SR
authors.lastname: Johnston
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D004351:Drug Resistance; D066246:ErbB Receptors / Q000502:physiology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D009857:Oncogenes; D013629:Tamoxifen / Q000378:metabolism / Q000627:therapeutic use*; D016211:Transforming Growth Factor alpha / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors