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Endocrine Therapy of Breast Cancer

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Annual rept. 17 May 2005-16 May 2006

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A recent controversy in the treatment of estrogen receptor positive ER breast cancers is whether an aromatase inhibitor, e.g., letrozole LET or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., -40 of tumors show cross resistance to TAM or an aromatase inhibitor on crossover. Only 50 of ER tumors respond to endocrine therapy. Currently, we fail to predict endocrine responsiveness in about 66 of ERPgR- progesterone receptor, 55 of ER-PgR, and 25 of ERPgR tumors. In this new Clinical Translational Research Award, we hypothesize that our analytical methods can extract expression profiles of breast tumors that define their responsiveness sensitive vs. resistant to endocrine therapy. These profiles, when combined with known predictiveprognostic factors, will support neural network and biostatistical classifiers or committee machines that predict each tumors endocrine responsiveness. Our objectives are to array breast cancer cases, build classifiers of endocrine responsiveness using microarray data, and validate these classifiers in independent data sets using mostly immunohistochemistry data IHC. IHC will be done on cases with definitive outcomes data. In the long term, we will design custom arrays for use in clinical practice. Genes will be further studied using cellular and molecular methods, and their role as therapeutic targets explored.

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  • Medicine and Medical Research

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