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    Preliminary experience with pure antiestrogens.

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    Authors
    Howell, Anthony
    Affiliation
    CRC Department of Medical Oncology, University of Manchester, Christie Hospital, United Kingdom. maria.parker@christie-tr.nwest.nhs.uk
    Issue Date
    2001-12
    
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    Abstract
    Endocrine therapy plays an important role in the management of all stages of breast cancer, and the development of effective endocrine therapies has focused on modifying the response of hormone-sensitive tumors to estrogen. The most widely used agents are the nonsteroidal antiestrogens or selective estrogen receptor (ER) modulators, the class to which tamoxifen, the standard in terms of antiestrogen therapy, belongs. Tamoxifen is effective in both adjuvant and first-line settings and is now used as prophylactic therapy in high-risk individuals. However, the partial agonist activity of tamoxifen on the uterus, coupled with "tumor flare" and the development of tamoxifen resistance, has limited its therapeutic utility. Attempts to eliminate the partial agonist activity of tamoxifen and increase its potency have led to the development of fulvestrant (Faslodex), the first in a new class of pure antiestrogens, the ER down-regulators. Fulvestrant has a high affinity for the ER compared with tamoxifen but has none of the agonist activities of tamoxifen. This new agent is showing promising clinical activity in the treatment of advanced breast cancer after tamoxifen therapy. Fulvestrant's lack of ER agonist activity may provide a longer duration of response compared with tamoxifen, as it did in a preclinical setting. Fulvestrant has demonstrated that it is at least as effective as the third-generation aromatase inhibitor anastrozole in patients whose disease has relapsed or recurred on prior endocrine therapy and is currently being evaluated in Phase III trials versus tamoxifen for the first-line therapy of advanced breast cancer. Future clinical studies will evaluate fulvestrant in adjuvant and neoadjuvant settings, together with its optimal sequencing in relation to tamoxifen and other endocrine therapies.
    Citation
    Preliminary experience with pure antiestrogens. 2001, 7 (12 Suppl):4369s-4375s; discussion 4411s-4412s Clin. Cancer Res.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/83233
    PubMed ID
    11916227
    Type
    Article
    Language
    en
    ISSN
    1078-0432
    Collections
    All Christie Publications

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