TY - JOUR
T1 - Neoadjuvant Endocrine Therapy As A Drug Development Strategy
AU - Ellis, Matthew J.
AU - Come, Steven
AU - Bissell, Mina
AU - Buzdar, Aman
AU - Santen, Richard
AU - Arteaga, Carlos
PY - 2004/1/28
Y1 - 2004/1/28
N2 - The aromatase inhibitors offer both toxicity and efficacy advantages over tamoxifen, but to date, their overall impact on breast cancer outcomes has been modest. Advanced breast cancer remains incurable, and for early stage disease, an improvement in survival with AI versus tamoxifen has yet to be demonstrated. Resistance to endocrine manipulation is at the core of the problem and must be overcome to make additional progress. A number of signal transduction inhibitors (STIs) are now under development as endocrine resistance modulators, including those targeting cyclooxygenase-2, HER1 and/or 2 kinase, mTOR, and farnesyl transferase. Developing STIs for this indication is a challenge, however, because we still do not have a clear understanding of the molecular basis of resistance. A complete understanding could translate into a series of endocrine therapy/STI combinations that would be tailored according to the biology of the individual tumor to achieve optimal efficacy and safety. The development of this strategy will require the ability to diagnose resistance mechanisms on a tumor-by-tumor basis, and this can only be attained through careful clinical investigation. Neoadjuvant endocrine therapy is an appealing context to conduct research in this area because clinical outcomes can be obtained within a few months of treatment, and repeated tumor sampling for biomarker analysis (pharmacodynamic tumor profiling) can be readily achieved. However, the optimal clinical investigative approaches, analytical techniques, and appropriate surrogate end points have yet to be identified and are the subject of several ongoing or planned clinical studies.
AB - The aromatase inhibitors offer both toxicity and efficacy advantages over tamoxifen, but to date, their overall impact on breast cancer outcomes has been modest. Advanced breast cancer remains incurable, and for early stage disease, an improvement in survival with AI versus tamoxifen has yet to be demonstrated. Resistance to endocrine manipulation is at the core of the problem and must be overcome to make additional progress. A number of signal transduction inhibitors (STIs) are now under development as endocrine resistance modulators, including those targeting cyclooxygenase-2, HER1 and/or 2 kinase, mTOR, and farnesyl transferase. Developing STIs for this indication is a challenge, however, because we still do not have a clear understanding of the molecular basis of resistance. A complete understanding could translate into a series of endocrine therapy/STI combinations that would be tailored according to the biology of the individual tumor to achieve optimal efficacy and safety. The development of this strategy will require the ability to diagnose resistance mechanisms on a tumor-by-tumor basis, and this can only be attained through careful clinical investigation. Neoadjuvant endocrine therapy is an appealing context to conduct research in this area because clinical outcomes can be obtained within a few months of treatment, and repeated tumor sampling for biomarker analysis (pharmacodynamic tumor profiling) can be readily achieved. However, the optimal clinical investigative approaches, analytical techniques, and appropriate surrogate end points have yet to be identified and are the subject of several ongoing or planned clinical studies.
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U2 - 10.1158/1078-0432.CCR-031202
DO - 10.1158/1078-0432.CCR-031202
M3 - Article
C2 - 14734497
AN - SCOPUS:1642446018
SN - 1078-0432
VL - 10
SP - 391s-395s
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1 II
ER -