The apoptotic action of estrogen following exhaustive antihormonal therapy: A new clinical treatment strategy

The apoptotic action of estrogen following exhaustive antihormonal therapy: A new clinical treatment strategy Original Research Article Pages 624-630 V. Craig Jordan, Joan S. Lewis, Clodia Osipo, Dong Cheng Close Close preview | Purchase PDF (192 K) | Related articles | Related reference work articles AbstractAbstract | Figures/TablesFigures/Tables | ReferencesReferences Summary 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. Article Outline Introduction Strategy for success Current concept of disease control Consequences of continuous antihormonal therapy Complex new concepts in estrogen signaling Integration of laboratory concepts into clinical practice Acknowledgements References