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Breast cancer is one of the most life threatening risks in women's life. In spite of considerable progress in its understanding and challenges, treatment is not yet the correct word to apply on this disease and losing life is the most foreseeing adventure in many patients. Although new gene therapy based approaches are looking for the cure of breast malignant cells, but using cytotoxic agents is currently the main chemotherapy approach to fight this problem. Effective chemotherapy treatment of breast cancer requires targeting the pathways that support the cell growth and proliferation. A good in vitro investigational model is essential to understand the process of carcinogenesis, risk and hazard mechanism of carcinogens, protection from carcinogens, mode of action and efficacy of novel and even in practice chemotherapeutic agents. The main part for any of these laboratory models is suitable cell lines to properly address the problem and goal of investigation. Estrogen Receptor (ER) is considered to cause different growth responses in ER-positive, normal, preneoplastic and neoplastic cells (DuMond et al., 2001; Roy & Cai, 2002; Welshons et al., 2003). One of the most significant researches in cancer treatment has been based on designing and studying the ER-antagonism effects of molecules on cells. This is important to select suitable cell lines for in vitro drug discoveries studies. Table 1 shows a list of epithelial breast cell lines with different expression in estrogen receptor. Intracellular enzymes responsible for the different consequences of receptors stimulations and signaling cascades are also under big considerations in fighting breast cancer cells. Dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolateNADP+ oxidoreductase) is an example of pivotal importance in biochemistry and medicinal chemistry. DHFR catalyzes the reduction of folate or 7,8-dihydrofolate to tetrahydrofolate and intimately couples with thymidylate synthase (TS). Reduced folates are carriers of one-

Remarks in Successful Cellular Investigations for Fighting Breast Cancer Using Novel Synthetic Compounds