Immunotherapy and Breast Cancer

Immunotherapy cancer treatments seem to be causing quite a sensation lately as evidenced by the increasing number of articles reporting seemingly miraculous results, both in the mainstream and scientific press. The concept of stimulating the body’s own defense system to not only eradicate disease, but also to prevent recurrence in the future is an attractive one. Before we get too carried away with the magic of immunotherapy, however, it is important to understand exactly what this means, how it works and, of particular interest to us here at the BCCRF, whether this is a valid treatment option for breast cancer.

Immunotherapy has been shown to drastically improve survival rates in certain patients with melanoma, bladder cancer, kidney cancer, non-small cell lung cancer and certain blood cancers, even in the metastatic setting. The main reason for this is that these types of cancers are more immunogenic and are defined as being “hot”. What this means is that the tumors contain higher numbers of infiltrating T-cells – a type of immune cell – that can be provoked by the treatment into killing the surrounding cancer cells. Cancers that respond well to immunotherapy also contain more mutations, enabling the body to identify them as foreign and thus target them for elimination. Even in these immunogenic cancers, only a minority of patients undergo a complete response, but for the more common, immunologically “cold” solid tumors, such as ovarian, prostate, pancreatic and most breast cancers, immunotherapy has not yet proven to be very effective.

Specific to breast cancer, several newer clinical studies have shown promise in using immunotherapy to improve outcomes for the triple negative (TNBC) subtype of the disease. TNBC typically has a poorer outcome because it tests negative for estrogen, progesterone and HER2 receptors, and hence cannot be treated with the existing effective medicines that target these receptors. Conversely, however, TNBC is the subtype most likely to have infiltrating T-cells, suggesting a more favorable immune response. In March 2019, the FDA approved the use of an immunotherapy drug called atezolizumab (Tecentriq) in combination with chemotherapy for treating certain inoperable metastatic TNBC patients. In these patients, their cancer cells try and hide from the immune system by presenting certain proteins on their surface to mimic healthy cells and avoid being identified and eradicated. This drug allows the T cells to attack the cancer cells by targeting these proteins and identifying them as abnormal.

A major challenge with drugs like atezolizumab is that they can create substantial side effects because they frequently attack normal cells as well. Typically, these manifest as skin reactions such as redness and blistering as well as flu-like symptoms, including fever, nausea and body aches. Researchers are seeking better ways to manage these side effects so that eventually, immunotherapy can be safely tested on patients with earlier stage disease and not just in the metastatic setting. Another crucial barrier that must be addressed and overcome is the high cost of these experimental treatments that insurance may not cover.

As exciting as the field of immunotherapy seems to be, much work remains in order to take advantage of it for breast cancer patients. Current studies are seeking ways to transform “cold” tumors into “hot” tumors to improve their immunogenicity. Also, research is being conducted to create potential cancer treatment vaccines, made up from parts of cancer cells or specific antigens (proteins that identify a cell as foreign) that, when injected into the body, would boost the immune system’s reaction to the tumor cells. In the meantime, the most important thing to remember is that journalistic articles touting the potentially miraculous effects of immunotherapy must be read with a grain of salt. Science is on the cusp of many brilliant discoveries in the fight against cancer but we, unfortunately, still have a long way to go before we can consider it won.

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