Researchers Identify Biomarker to Predict Immunotherapy Response in Patients With Breast Cancer

Researchers have identified a biomarker that could predict responses to immunotherapies in patients with breast cancer. The biomarker, called the Major Histocompatibility Complex Class II protein (MHC-II), was previously shown to be a predictor of immunotherapy responses in patients with melanoma.

In a recent study published in Clinical Cancer Research, a journal of the American Association for Cancer Research, MHC-II showed potential, when expressed on breast cancer cells, for early-stage, triple negative breast cancer (TNBC) and high-risk, estrogen receptor-positive breast cancer (HR+).

“With these newer therapies, because of the potential for side effects and the high costs associated with the drugs (the goal) is to really try to personalize medicine and care for patients,” said Justin Balko, Doctor of Pharmacy who holds a post doctorate and is an assistant professor of medicine and pathology, microbiology and immunology at the Vanderbilt University Medical Center, in an interview with CURE®. Balko conceived and designed the study.

“When we started years ago in melanoma, we were interested in ‘What are some markers that might help us decide whether or not a patient was likely to get a benefit from these immunotherapy drugs?’ And so, we've learned a lot over the years, and what we've essentially found (is) that there was this one marker that we can very easily test on in cancer cells by a standard that's called a pathology test, or immunohistochemistry, that would give us a pretty good idea on the likelihood of whether or not that patient would respond.”

This research began in melanoma, said Balko, and is now being applied to breast cancer in anticipation of the immunotherapy drugs that will be used for patients in the future, but are waiting for approval from the Food and Drug Administration (FDA). If researchers are able to identify which patients can benefit from immunotherapies, it will benefit breast cancer research as a whole, so future clinical trials can be specifically aimed only at the patients who are or aren’t going to benefit from certain drugs.

“The most important takeaway, I think, is that these are preliminary results, we haven't validated them, or (had) what we call a prospective, randomized phase 3 trial,” said Balko. “But they are very encouraging, because what we found is that from big trials, only about 15% of patients that are treated with these drugs actually need the drug and or benefit from the drugs.”

To conduct their research, the investigators performed a retrospective – meaning they used tissue that had already been used in a previous clinical trial – analysis of three groups of patients with breast cancer: patients with non-immunotherapy treated breast cancer; patients with TNBC who were treated with Imfinzi (durvalumab) and standard chemotherapy; and patients with HER2-negative breast cancer who were treated with either standard chemotherapy alone or with Keytruda (pembrolizumab).

They observed that MHC-II was expressed in a subgroup of TNBC and HR+ breast cancers, demonstrating its potential as a pan-cancer biomarker for anti-PD-1 or anti-PD-L1 immunotherapies, based on prior findings in melanoma and Hodgkin’s lymphoma.

The results are promising, said Balko, and much needed in the field of breast cancer research as medical care costs continue to rise. “They're very powerful drugs, and they've helped many, many patients. But the problem is that because they're immune mediated, a small percentage of patients can have what's called immune-related adverse events,” he said.

“And those while they're generally rare, they can be significant. And a big part of what our laboratory’s research is also trying to understand (is) why these immune related adverse events occur. They can range from affecting any organ system – patients can be type one diabetics and require insulin for the rest of their lives after being treated with these drugs. Again, this is very rare, but they're significant toxicities that the patient might have to live with for the rest of their life.”

In terms of next steps, Balko emphasized that researchers need to develop a clinically standardized test to verify how stable the marker is over a long period of time and how consistent the staining is. He added that there is a need for additional work on establishing a standardized scoring metric.

“And then above and beyond those sorts of technical things, what we need to do is have a very large phase 3 trial,” said Balko. “So we have to do that prospectively versus retrospectively, which is what we did.”

Read more: FDA Approves Keytruda/Chemo for Triple-Negative Breast Cancer

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