Nanotechnology based docetaxel: upcoming avenue for breast cancer management

Despite decades of epidemiological, laboratory, and clinical research, incidence of breast cancer continues to rise. Breast cancer is a clinically and biologically heterogeneous disease, with several recognized histotypes and molecular subtypes having different underlying mechanisms, responses to prognosis, and treatments. Breast cancer positions itself to the second slot in occurrence after lung cancer in women when seen globally. It tops the list for cancer among the Indian women with a mortality rate of 12.7 per 100,000 women as documented in the National Cancer Registers. The American Cancer Society reported 40,610 deaths in the United States alone in the year 2017. Furthermore, advanced stages of breast cancer are often associated with metastasis to the bones, lungs, liver, and brain. Anthracyclines and taxanes are the two classes of drugs often prescribed by physicians in better management of metastatic breast cancer. However, till date, scientific investigations have concluded taxane-based chemotherapy to be highly effective in breast cancer progression. Docetaxel (DTX), a taxane derivative, has shown efficacy even in patients developing resistance to anthracycline treatment. However, DTX undergoes P-gp efflux resulting in high incidence of drug resistance in cancer cells. Marketed formulation of DTX (Taxotere) is often associated with severe side effects which are partly due to DTX and partly due to excipients/solvent used in its formulation. In order for a drug to be effective in surmounting physiological tumor barriers, it must reach the microenvironment of the tumor site at an MIC specific for the cancer cells. Exposure of cancer cells to subtherapeutic concentration (below MIC) of a drug can lead to resistance. On the other hand, high systemic concentrations required to achieve MIC at tumor site trigger toxicity, obstructing the clinical utility of chemotherapeutic agents. Numerous studies support the utilization of nanotechnology as a platform through which chemotherapeutics like DTX can reach tumor tissue, in a controlled manner, both via active and passive (enhanced permeation and retention) targeting. Targeted delivery of chemotherapeutic loaded nanoparticles helps to (1) ensure achievement of high drug load at the target site and (2) avoid development of resistant cancer cells. This book chapter will discuss in detail about breast cancer, its treatment strategies with special reference to DTX-based nanotreatment options for better management of breast cancer, and its metastasis.