| Overcoming Endocrine Therapy Resistance in Breast Caner |
| Tae Hyun Kim |
| Department of General Surgery, Busan Paik Hospital, Inje University, Busan, Korea |
| 유방암에서 내분비 치료의 내성 극복 |
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김태현 |
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인제대학교 부산백병원 외과 |
| Corresponding Author:
Tae Hyun Kim ,Tel: +82-51-890-6352, Email: kitah@hanmail.net |
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Received: November 20, 2009; Accepted: December 23, 2009. |
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| ABSTRACT |
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Estrogens are steroid hormones that regulate growth, differentiation and function in a broad range of target tissues in the
body and the exposure to estrogens is an important determinant for risk of breast cancer. The biologic effects of
estrogens are mediated through estrogen receptor (ER) αand β. Endocrine therapies first used more than 100 years ago
and progressed toward an understanding of antigestrgen action and successful clinical development of antiestrogen for
the treatment of breast cancer. Endocrine therapies are the most effective treatment for breast cancer expressing ER but
resistance remained major problem.
Endocrine therapy resistance is commonly associated with ER mutation, Aromatase mutation, loss of ER, pharmacogenetic
change, change of coactivators and corepressors, and crosstalk between ER and growth factor pathways.
Preclinical models demonstrate that growth factor receptor tyrosine kinase inhibitors can restore Tamoxifen resistance and
delay acquired resistance to estrogen deprivation therapy. Several clinical trials have been reported the results about
combined treatment of endocrine agents and target agents to overcome or delay endocrine resistance. The addition of
trastuzumab to the aromatase inhibitor and tyrosine kinase inhibitor lapatinib to letrozole has significantly improved
progression-free survival in ER-positive/HER2-positive metastatic breast cancer. Epidermal growth factor receptor (EGFR)
inhibitor gefitinib combined with endocrine therapies demonstrated small benefit in ER-positive metastatic breast cancer.
Target agents to downstream signal pathway, such as mammalian target of rapamycin (mTOR) inhibitor and
farnesyltransferase inhibitors (FTIs), showed the possibility for combine aged to prevent endocrine resistance.
We need to understand and evaluate various signaling elements from multiple networks that crosstalk with ER. Combined
therapy with selected targeted agents remains a promising approach to enhancing the efficacy of current endocrine
therapies for breast cancer. |
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