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Combining Immunotherapy and Radiation Could Improve Treatment Outcomes for Triple-Negative Breast Cancer

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Combining immunotherapy and radiation may help treat triple-negative breast cancer (TNBC), a subtype known for its limited treatment options, a recent study suggests.

In the study, published in Cancer Cell in January,

a team of researchers at Cedars-Sinai analyzed the combination of pembrolizumab, an immunotherapy drug known as Keytruda, with radiation therapy to identify patient response and understand changes in TNBC tumor cells from 34 patients. The study’s findings categorized patients into three groups: nonresponders, immediate responders, and delayed responders, each exhibiting different immune responses to the combined therapies.

“We found that roughly one-third of these [TNBC] patients showed indications they were benefiting from the radiation therapy,” says Stephen Shiao, MD, PhD, the codirector of the cancer therapeutics program at Cedars-Sinai Cancer in Los Angeles.

An Aggressive Form of Breast Cancer

According to the Centers for Disease Control and Prevention (CDC),

the term “triple-negative breast cancer” refers to the fact that these cancer cells lack receptors for estrogen, progesterone hormones, and the HER2 protein — all receptors needed for common cancer treatments to grab onto a cancer cell and begin destroying it. Since TNBC lacks these avenues for treatments to interact with the cancer cells, these tumors tend to grow and spread rapidly with fewer treatment options than other types. TNBC makes up about 10 to 15 percent of breast cancers, and most patients end up needing a presurgical chemotherapy or immunotherapy to shrink their tumors, according to the American Cancer Society.

“Unfortunately, only 20 to 30 percent of patients respond to immunotherapy on its own. Combining it with chemotherapy boosts response to 60 percent but exposes patients to significant toxicity,” said Dr. Shiao in a press release.

The Body’s Response to Treatment

Janice N. Kim, MD, an associate professor in the department of radiation oncology at the University of Washington’s Fred Hutchinson Cancer Center in Seattle, who was not involved with the study, says that radiation kills tumor cells, signaling the immune system to attack. But cancer cells can trick the immune system into not attacking them so they can survive and spread. Immuno-checkpoint inhibitors are medications that prevent evasive cancer cells from avoiding or disabling immune cells, instead revving up immune cells to attack tumor cells, particularly in TNBC.

For the study, the research team analyzed tumor biopsies at various treatment stages to see how the therapy changed the organization of cells in the tumor environment. Using different molecular technologies, they clarified what kinds of cells were in the tumors during the treatment and how they reacted to the therapy. They also assessed many proteins on the surface of cells all at once, which showed how immune and cancer cells were arranged in the tumor.

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