**3. Pathogenesis**

Breast cancers typically begin as ductal hyperproliferation and progress to benign tumours or even metastatic carcinomas as a result of continuous stimulation by carcinogenic agents. Breast cancer initiation and progression are influenced by tumour microenvironments such as stromal effects and macrophages. When only the stroma, not the extracellular matrix or the epithelium, was exposed to carcinogens, the mammary gland of rats may be driven to neoplasms. Macrophages may create a mutagenic inflammatory microenvironment, allowing cancer cells to avoid immune rejection and increase angiogenesis. The normal and tumour-associated

*The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast… DOI: http://dx.doi.org/10.5772/intechopen.100143*

#### **Figure 1.**

*The risk factors of breast cancer.*

microenvironments exhibit different DNA methylation patterns, suggesting that epigenetic changes in the tumour tissue may promote tumorigenesis. Cancer stem cells (CSCs), a new type of malignant cell seen in tumours, have been linked to tumour genesis, migration, and relapse. This minor group of cells can auto renew and is resistant to chemotherapy and radiation. They may be produced from stem

cells or progenitor cells in normal tissues. Ai Hajj was the first to identify breast cancer stem cells (bCSCs), demonstrating that as few as 100 bCSCs can create new tumours in infected mice. Luminal epithelial progenitors are more likely than basal stem cells to give rise to bCSCs. Wnt, Notch, Hedgehog, p53, PI3K, and HIF are all signalling pathways involved in the auto-renewal, multiplication, and migration of bCSCs. However, more research is needed to fully comprehend bCSCs and create ingenious ways for their eradication. The cancer stem cell theory and the stochastic theory are two distinct hypotheses for breast cancer initiation and progression. All tumour subtypes, according to the cancer stem cell theory, are derived from the same stem cells or transit-amplifying cells (progenitor cells). Various tumour features will result from acquired genetic and epigenetic alterations in stem cells or progenitor cells (**Figure 2**). According to the stochastic theory, each tumour subtype begins from a single type of cell (stem cell, progenitor cell, or differentiated cell) (**Figure 2**). Any breast cell can acquire random mutations over time, eventually transforming it into a tumour cell if enough mutations are accumulated. Despite the fact that both theories are backed up by evidence, neither can adequately explain the origins of human breast cancer [7].
