New Endocrine Strategy to Prevent Breast Cancer Progression
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Endocrine therapy is commonly used to prevent breast cancer progression, but most patients eventually develop hormone-resistant disease. This failure of hormone therapy often associates with gene abnormalities found in some breast cancers. The growth of breast cells is regulated by hormones and growth factors which react with specific receptor molecules. Alterations in specific genes in breast cancers lead to the production of multiple copies of growth factor receptors in two-thirds of breast cancers. These alterations play an important role in the development and progression of cancer and appear to predict a poor response to endocrine therapy. This project will assess mechanisms by which altered genes affect the pathogenesis and hormonal sensitivity of breast cancers, and the results may lead to improved prevention strategies. Aims of this project are: 
 
 
 
 
 
 
 
 1) To evaluate the potential interaction of altered growth factor receptors with receptors for estrogen hormones in the development of hormone resistance in human breast cancer. Using preclinical models, cells with low levels of growth factor receptor and matched cells with high levels of growth factor receptor will be tested for their differential sensitivity to estrogen and to antiestrogen drugs which block estrogen effects, such as tamoxifen. Experiments will be done in vitro and in vivo, utilizing a mouse model. In addition, we will assess the advantage of antiestrogen therapy in combination with protein antibodies which counteract the effects of specific growth factor receptors, including the HER-2 growth factor receptor. 
 
 
 
 
 
 
 
 2) To investigate effects of high levels of growth factor receptors on the production and biologic action of receptors for estrogen in human breast cancer cells. Effects of the growth factor, heregulin, on interaction of estrogen receptor with DNA-binding sites in the nucleus of breast cancer cells will also be investigated. 
 
 
 
 
 
 
 
 3) To determine effects of estrogen and antiestrogens on the production of growth factor receptors and growth factors, such as heregulin, in human breast cancer cells. Heregulins may be induced by estrogens in breast cancer cells. This hypothesis will be tested directly in breast cells. Regulation of the production and activity of growth factor receptors, in turn, by estrogens and antiestrogens will be further evaluated. 
 
 
 
 
 
 
 
 4) To use clinical specimens to evaluate the relationship of heregulin and growth factor receptors to estrogen receptor and development of the estrogen-independent state in human breast cancer. Data on levels of growth factor receptors (HER-1, HER-2, HER-3, HER-4 receptors), heregulin growth factor and estrogen receptors will be correlated with independent data on the growth of actual tumors and the clinical course of patients in the clinic. 
 
 
 
 
 
 
 
 These studies may help to guide patient management decisions to prevent disease progression and, possibly, lead to alternate targeted strategies in breast cancers with overexpression of growth factor receptors.