Immunotherapy may offer a glimmer of hope to patients with triple negative breast cancer



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Breast Cancer Review
Breast Cancer Review

Breast cancer is the most common cancer among women in the world. More than two million new cases have been diagnosed in 2018. There are different types of breast cancers, mainly classified according to the expression of certain proteins such as estrogen receptors (ERs), progesterone receptors (PR) and Her2 (human epidermal growth factor receptor 2).

Drugs have been specifically developed to target these proteins on cancer cells. For example, women with breast cancer with a positive ER are treated with a drug called Tamoxifen that blocks ER action and that gives hope to millions of women. Some breast cancers, however, do not express any of these three proteins (ER, PR or Her2) and are classified as triple negative breast cancer (TNBC).

TNBC is a notoriously aggressive form of breast cancer and people who suffer from it are unlikely to survive. This is more likely to happen in younger women. This type of breast cancer accounts for about 15% of all breast cancer cases. Its incidence in India is however higher (27.9%) compared to other regions of the world.

Traditionally, chemotherapy, which involves administering a range of drugs to prevent cancer cells from growing in an uncontrolled manner, was the TNBC treatment standard. Despite the treatment, TNBC patients have high rates of recurrence of the disease, which unfortunately leads to premature death. There is therefore an urgent need for better treatments in the treatment of TNBC.

Immunotherapy, which strengthens the body's immune system, has shown great promise in treating some cancers and is now recognized as a potential therapeutic approach in TNBC. It uses the body's own molecules or synthetic substances that strengthen or restore the immune system.

One type of immunotherapy recently developed uses a class of drugs called checkpoint inhibitors, which exploits key T-cell surface molecules, which are a major weapon in the body's immune system. James P Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine 2018 for their work leading to the discovery of new molecules that led to the development of immunotherapy.

A new study recently published in the New England Journal of Medicine (NEJM) by Dr. Peter Schmid of the Barts Cancer Institute at Queen Mary University in London and colleagues revealed that combining immunotherapy with chemotherapy could improve the results of some advanced triple negative treatments. breast cancer patients.

More than 900 patients with untreated metastases (where the cancer spread to other parts of the body, such as the lungs) were enrolled in a Phase III clinical trial and randomly assigned to Neb -Paclitaxel, a chemotherapeutic drug used to treat breast cancer. with a placebo (not immunotherapy) or in combination with Atezolizumab, a drug belonging to the class of point-control inhibitory immunotherapies.

In the body, immune T cells express a surface molecule called PD-1 that can bind to another molecule called PD-L1 present on other cells. This attachment tells the T cells that the other cell should not be destroyed and thus prevents them from being attacked by the immune system. Some cancer cells very cleverly exploit this in the manner of a Trojan horse by having more PD-L1 molecules on their surface and thus escape an immune attack. The immunotherapy drug, Atezolizumab, works by blocking PD-L1 molecules on cancer cells and thus prevents them from transmitting erroneous signals to immune cells.

However, this study has significant disadvantages. Combination therapy was found to increase mean survival at 25 months versus 15.5 months. But the cancer cells had to have on their surface a high level of PD-L1 molecules, which may not be in all patients. This means that it is necessary to check the status of the PD-L1 receptor in patients before starting treatment.

In addition, it must be taken into account that the side effects associated with combination therapy are more serious than those with single-agent chemotherapy. In addition, the cost of such a personalized immunotherapy could be extremely high, a treatment cycle being Rs. 1 lakh to Rs.13 lakh.

Immunotherapy is still developing in developing countries like India and is now available in some treatment centers, mainly for solid tumors such as prostate, breast, kidney, colon, hepatocellular carcinoma , colorectal, oral, pulmonary and ovarian cancer. Although this is only the first major clinical trial involving immunotherapy and more studies are needed, the positive results cast a glimmer of hope on patients with TNBC.

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