%0 Journal Article
%T Transforming growth factors-¦Â are not good biomarkers of chemopreventive efficacy in a preclinical breast cancer model system
%A JoAnne Zujewski
%A Anika Vaughn-Cooke
%A Kathleen C Flanders
%A Michael A Eckhaus
%A Ronald A Lubet
%A Lalage M Wakefield
%J Breast Cancer Research
%D 2000
%I BioMed Central
%R 10.1186/bcr273
%X Chemoprevention has been defined as the use of noncytotoxic nutrients or pharmacologic agents to enhance intrinsic physiologic mechanisms that protect the organism against the development of mutant clones and their progression to malignant cancer. In a recent landmark trial, tamoxifen, a hormonally active selective estrogen receptor modulator (SERM), was shown to decrease the risk of invasive breast cancer by 49% in asymptomatic, but at-risk women [1]. The search is now on for agents with improved risk-benefit profiles, and for agents that will prevent the subclass of estrogen receptor-negative tumors, the incidence of which was unaffected by the SERMS. Retinoids have already shown potential in this regard [2,3,4,5,6,7]. Because it will not be possible to test many agents in large randomized clinical trials, efforts are underway to develop useful tissue-based surrogate end-point biomarkers that can be used to select only the most promising agents (and doses) for large-scale trials.Provocative mechanistic connections have been made between the steroid hormone superfamily, including the SERMS and retinoids, and the TGF-¦Â family of multifunctional growth factors [8]. The TGF-¦Â system has tumor suppressor activity, and loss of TGF-¦Â response is associated with advanced disease in many human tumor types, including the breast [9,10]. Conversely, experimental overexpression of TGF-¦Â in the mammary gland protects against tumorigenesis [11]. This strongly suggests that interventions that enhance TGF-¦Â function early in tumorigenesis could delay or prevent the course of the disease. SERMs such as tamoxifen can upregulate TGF-¦Â production and activation by many cell types, including human breast cancer cell lines [12,13,14,15]. Similarly, retinoids can upregulate TGF-¦Â production and activation, both in cell culture and in rats in vivo [16,17]. It is plausible, therefore, that upregulation of endogenous TGF-¦Â could contribute to the chemopreventive efficacy of SERMs and retino
%K antiestrogens
%K breast cancer
%K chemoprevention
%K retinoid
%K transforming growth factor-¦Âs
%U http://breast-cancer-research.com/content/3/1/66