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Immunotherapy may offer a triple negative breast cancer patient



Breast cancer examination
Breast cancer examination

Breast cancer is the most common diagnosed in two million new cases diagnosed in 2018. Different types of breast cancers, mainly classified based on certain proteins such as Estrogen Receptor (ER), Progesterone Receptor (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 ER is called Tamoxifen which blocks the action of ER and has given hope to millions of women. Some breast cancers, however, do not express any three proteins (ER, PR or Her2) and are classified as Triple Negative Breast Cancer (TNBC).

TNBC is a very aggressive form of breast cancer and those suffering from it have slim chance of survival. It is more likely to occur in women. This is about 15% of total breast cancer cases. Its incidence in India, however, is higher (27.9%) compared to other regions of the world.

Traditionally, chemotherapy which involves administration of a range of drugs to prevent cancer cells from uncontrolled growth has been the standard of care for TNBC. Despite treatment, TNBC patients showed high rates of rehabilitation of the disease which unfortunately led to untimely death. Hence there is an urgent need for better therapies in treating TNBC.

Immunotherapy, which boosts the immune system of the body, has been shown to be a great deal of promise and is a potential therapeutic approach in TNBC too. It uses the body's own molecules or synthetically produced substances that enhance or restore immune systems.

One recently developed type of immunotherapy called checkpoint inhibitors, which are key surface molecules on T cells, which is a major weapon of the human body's immune system. James P Allison and Tasuku Honjo were awarded the 2018 Nobel Prize in Physiology or Medicine for their work led to the discovery of novel molecules which led to the development of immunotherapy.

A published recently in the New England Journal of Medicine (NEJM) by Dr. Peter Schmid of the Barts Cancer Institute, Queen Mary University of London, and colleagues, has found that combining immunotherapy with chemotherapy can improve triple negative breast cancer patients.

More than 900 patients with untreated metastatic disease (where the cancer has spread to the body like the lungs) TNBC was used as a phase III clinical trial, and a chemotherapeutic drug used to treat breast cancer either with a placebo (no immunotherapy drug) or a class of immunotherapy drugs.

In the body, immune T cells present on other cells called PD-L1 present on other cells. This attachment conveys to T cells that are not to be destroyed and therefore are being attacked by the immune system. Some cancer cells are very cleverly exploited in this Trojan horse by having more PD-L1 molecules on their surface and hence the escape an immune attack. The immunotherapy drug, Atezolizumab, works by blocking PD-L1 cells on cancer cells and thus from conveying wrong signals to immune cells.

However, there are significant drawbacks in this study. The combination of therapy was found to increase the average survival to 25 months as against 15.5 months. But cancer cells have high levels of PD-L1 molecules on their surface which may not be in all patients. This means that there is a status of PD-L1 receptor in patients before commencing the therapy.

In addition, it must be considered that side effects are more severe than for single agent chemotherapy. Also the cost of personalized immunotherapy can be extremely high with one round of therapy being Rs. 1 lakh to Rs.13 lakh.

Immunotherapy is still evolving in developing nations like India and is now a little treatment center and that too is primarily for solid tumors like prostate, breast, renal, colon, hepatocellular carcinoma, colorectal, oral, lung and ovarian. Although this is the only the first large clinical trial involving immunotherapy and more studies are required, the findings are positive for a ray of hope for TNBC patients.


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