title: The apoptotic action of estrogen following exhaustive antihormonal therapy: a new clinical treatment strategy.
abstract: Long-term antihormonal therapy is effective at controlling the recurrence of estrogen receptor (ER)-positive breast cancer, but there may be unanticipated consequences for the development of new forms of drug resistance. Laboratory studies of exhaustive antihormonal therapy demonstrate there are at least two phases of resistance to selective ER modulators (SERMs; tamoxifen and raloxifene) and to estrogen withdrawal (aromatase inhibitors). In Phase I drug resistance, estrogen or a SERM promote tumor growth, but in Phase II drug resistance estrogen induces apoptosis. Understanding of the new biology of estrogen action has clinical relevance. There are paradoxical interactions between fulvestrant and postmenopausal levels of estrogen that cause robust growth of Phase II tamoxifen resistance or autonomous aromatase-resistant tumors. These new data suggest a rational approach for the treatment of patients with ER-positive breast cancer that have failed exhaustive antihormonal treatment. Low-dose estrogen could be used to debulk patients followed by fulvestrant in a low estrogen environment (aromatase treatment) to maintain tumor control.
authors.affiliation: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. v.craig.jordan@fccc.edu
authors.forename: V Craig
authors.initials: VC
authors.lastname: Jordan
authors.forename: Joan S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Clodia
authors.initials: C
authors.lastname: Osipo
authors.forename: Dong
authors.initials: D
authors.lastname: Cheng
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators