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.
“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
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.
“I feel this is a great study, very promising,” Dr. Kim says. “Breast cancer in general is never homogenous. Some cells are really strong, and some are not as strongly triple negative, and that’s why we don’t always have a complete response to pre-op therapies. So, maybe with the radiation, they found that synergy causing that huge change in that environment. [And] maybe that, together with immune therapy, will lead to a bigger response of tumor killing.”
Kim is also optimistic about the study because she suspects that when a treatment combines radiation and certain drugs that boost the immune system, it can help the body’s defense cells not only fight the cancer in one area but also work against the spread of the disease throughout the body. This might mean that care teams won’t have to rely as much on strong treatments like chemotherapy before surgery, making the overall treatment process gentler for patients. Some patients who are identified as highly reactive to radiation and immunotherapy might be offered this targeted approach and not need chemotherapy.
More Representation Is Needed
The lack of clinical trials in this line of inquiry, as well as the lack of patient representation in those trials, continues to raise key questions, notes Kim. “TNBC is a very aggressive breast cancer, so we need more robust data to make sure the medical oncologists are on board,” she says. “And unfortunately, TNBC is often seen in more marginalized populations. This is not a patient cohort that normally has the resources and access to these studies. Hats off to Cedars-Sinai. This is not an easy feat, and the fact that they got 34 patients is amazing. But I do think there are going to be some challenges because this is a group that does not always have the resources and access.”
Lingering Questions, and What’s Next
While the research underscores the potential benefits of combining radiation therapy and immunotherapy, particularly when researchers profile each individual’s cancer cells, the team calls for continued scrutiny and collaboration within the scientific community to ensure robust and reliable advancements in the field.
“We are now trying to identify biomarkers to categorize patients into those that would likely benefit from the combination therapy,” says Simon Knott, PhD, a codirector of the Applied Genomics Shared Resource at Cedars-Sinai Cancer and a senior author of the study.
They also plan to conduct another study for patients who they find likely won’t respond well to the treatment. In that second study, they will use information they learned from the first to target the pathways in this patient population’s immune system that are resisting treatment. There are also larger studies underway to address questions about how much treatment to give and when. All this research will fine-tune experts’ understanding of the treatments to make them as effective as possible, for as many different patients as possible.
The ability to customize treatment according to the patient’s immune environment is promising, Dr. Knott says, but practitioners also need a quick test for it, such as a blood test. These problems must be solved before the treatment approach is rolled out in clinics.
Still, Knott says, “Our findings are a crucial first step in tailoring treatment in TNBC based on the immune makeup of an individual patient’s tumor.”
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