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In many cases of the disease, metastatic breast cancer does not respond to hormone (endocrine) therapy, thus necessitating the use of cytotoxic chemotherapeutic agents. These include anthracyclines, taxanes, alkylating agents, fluoropyrimidines, antimetabolites, vinca alkaloids, platinum-based agents, and others including the newly approved Eribulin. Taxanes (such as paclitaxel) and Eribulin are mitotic inhibitors; specifically, they disrupt the function of microtubules, although taxanes and Eribulin do so through different mechanisms. Anthracyclines (such as doxorubicin) induce DNA intercalation; and antimetabolites interfere with DNA synthesis. Of these, the taxanes and the anthracyclines are the most commonly used chemotherapeutic agents in the treatment of metastatic breast cancer.

Despite the multitude of chemotherapeutic agents available to treat metastatic breast cancer, treatments are still focused on palliative care; to date there is no cure for metastatic breast cancer. The failure of traditional chemotherapy to cure breast cancer is due largely to development of drug resistance by the cancer. According to Gradilone et al, resistance to anthracyclines are responsible for over 90% of treatment failures in patients with metastatic breast cancer; McGrogan et al also point out that resistance to taxanes is becoming increasingly common. Mechanisms of resistance to chemotherapeutic agents by cancer cells include efflux of the drug from the cell, modification of the binding site targeted by the specific chemotherapeutic agent, enzymatic drug detoxification, and DNA repair.

Of these, the most widely studied is efflux of the drug via transport proteins, whereby cancer cells use ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), multidrug-resistant protein 1 (MRP1), and breast cancer resistance protein (BCRP), to pump xenobiotics out of the cell, preventing accumulation of the chemotherapeutic agent at levels high enough to kill the cell. Moreover, alterations to ABC transporters can lead to excessive efflux of structurally unrelated drugs, a phenomenon known as multidrug resistance (MDR), which is the primary cause of failure of chemotherapy for most cases of metastatic breast cancer.