## 5 Breast Cancer and Current Treatment Strategies  
Cancer refers to a group of diseases marked by uncontrolled cell growth and division, resulting in the formation of a primary tumor that invades and damages surrounding \begin{table}
\begin{tabular}{c c c} \hline
**Ligand\(\backslash\)Target Structure** & **Unknown** & **Known** \\ \hline \multirow{4}{*}{unknown} & HTS & De Novo Design \\  & & \\  & & \\  & & \\  & & \\  & & \\  & & \\  & & \\  & & \\ \end{tabular}
\end{table} 
Table 4: Techniques for lead identification and optimization based on the knowledge of ligand and target structures. \begin{table}
\begin{tabular}{c c c} \hline
**Hit** & **Lead** & **Drug** \\ \hline \multirow{4}{*}{bring the pharmacophore} & M\({}_{\text{w}}\) \(<\) 300 Da & M\({}_{\text{w}}\) \(<\) 500 Da \\  & logP \(<\) 3 & logP \(<\) 3 \\  & up to 3 H-bond donors & up to 5 H-bond donors \\  & up to 3 H-bond acceptors & up to 10 H-bond acceptors \\  & positions for replacement & up to 10 rotatable bonds 10 \\  & affinity \(<\) 10 \(\upmu\)mol/L & affinity \(<\) 10 nmol/L \\ \hline \end{tabular}
\end{table} 
Table 3: Features of the three generations of molecules: hit, lead, and drug. tissues. It can also spread to other parts of the body through a process called metastasis, responsible for 90% of cancer-related deaths globally [188]. Breast cancer (BC) can occur in women of any age after puberty and is widespread globally. According to the World Health Organization (WHO), as reported on 13 March 2024, BC affected 2.3 million women and caused 670,000 deaths in 2022 [189]. Factors that increase the risk of breast cancer include age, obesity, excessive alcohol consumption, a family history of breast cancer, a history of radiation exposure, reproductive history (such as the age at first menstrual period or first pregnancy), tobacco use, and postmenopausal hormone status [190]. Unfortunately, half of BC cases are not associated with specific risk factors, with the exceptions being age (over 40 years) and gender (female). In breast tissue, the hormones estrogen and progesterone are primary regulators of cell proliferation and differentiation [191]. These hormones pass through the cell membrane and bind to their corresponding receptor monomers--ERs and PRs. Upon binding, the receptors dimerize and are transported into the nucleus, where they activate signaling pathways. Extracellular estrogens bind to membrane receptors and activate the PI3K/AKT signaling pathway, which controls various cellular processes such as cancer formation and progression, apoptosis, angiogenesis, and cell cycle progression [192]. As a result, hormone therapy, including ER blockers (also known as antiestrogens) and aromatase inhibitors (AIs), is a major therapeutic strategy (Figure 4) [193]. Antiestrogens are medications that prevent transcriptional stimulation by estrogen receptor complexes [194]. There are two main types of antiestrogens: (1) nonsteroidal antiestrogens, also known as selective estrogen receptor modulators (SERMs), and (2) pure antiestrogens, which are analogs of natural hormones with long, flexible side chains at the C-7 position. Figure 4: The pathways involved in estrogen-mediated carcinogenesis are illustrated. The yellow ellipses highlight different classes of medications and their targets. Aromatase inhibitors block the enzyme aromatase, which converts androgens, into estrogens, while antiestrogens prevent the activation of transcription in cells caused by estrogen–receptor complexes. High estrogen levels contribute to carcinogenesis through two mechanisms: genotoxic, involving DNA mutations and increased cell proliferation (the upper pathway in the enclosed rectangle), and nongenotoxic, involving mutagenic species generated from estradiol metabolism that undergo oxidation, producing reactive oxygen species that cause oxidative stress and cell damage (the lower pathway in the enclosed rectangle).