Immune-Based Therapy Shows Promise Against Advanced Breast Cancers

An experimental therapy that harnesses the body’s tumor-fighting immune cells may be effective for some women with advanced breast cancer, early research suggests.

The findings come from an ongoing trial at the U.S. National Cancer Institute (NCI). It is testing a new approach to treating women whose breast cancer has spread throughout the body and is not responding to standard therapies.

Researchers call it a “highly personalized” form of immunotherapy that uses patients’ own immune system T cells to target their genetically unique cancer.

At this point, the team is reporting on only six women who’ve undergone the immunotherapy. Three responded and have been cancer-free for at least 3.5 years, according to findings published online Feb. 1 in the Journal of Clinical Oncology.

“This is highly experimental and is not yet approved by the Food and Drug Administration,” stressed senior researcher Dr. Steven Rosenberg, chief of the surgery branch at the NCI’s Center for Cancer Research.

But, he said, the initial findings offer “hope.”

Rosenberg said the results also go against the traditional “dogma” that breast cancer typically does not illicit much of an immune response — and, therefore, is usually not susceptible to immunotherapy.

Immunotherapy refers to any treatment that enlists immune system defenses to battle a disease. There are various forms of cancer immunotherapy already approved, but not all types of cancer respond well to those drugs.

Melanoma is a prime example of a cancer that responds well, Rosenberg said. Melanoma tumors carry many mutations, which can draw a strong immune reaction. And immunotherapy (particularly drugs called checkpoint inhibitors) has transformed the treatment of advanced melanoma.

In contrast, breast tumors contain relatively few mutations, and there has been limited success so far in treating advanced breast cancer with available immunotherapies. Checkpoint inhibitors are approved for certain women with an aggressive subtype of breast cancer known as triple-negative.

The approach Rosenberg’s team is developing is different. “We’re using the patient’s T cells as the drug,” he said.

The researchers have so far used the approach to treat patients with advanced melanoma and certain other cancers, including a rare gastrointestinal cancer.

Specifically, the treatment relies on tumor-infiltrating lymphocytes — T cells found in and around a tumor. The idea is that, if those T cells are indeed reactive against the tumor, that can be enhanced and used as a weapon.

The current study involved 42 women with metastatic breast cancer that was not responding to conventional treatments. Metastatic means their cancer had spread. Each patient underwent surgery to remove a tumor sample, which the researchers genetically sequenced to identify its mutations.

They then isolated T cells from the tumor and, in the lab, tested the cells’ reactivity to the tumor’s specific mutations.

It turned out that in most patients — 67% — those T cells were reactive to at least one of their tumor mutations.

Why weren’t those T cells killing the tumor?

The problem, as Rosenberg explained it, is that tumors have tricks for evading the immune response. So those tumor-infiltrating T cells were not enough on their own.

The immunotherapy tactic seeks to help. The patient’s reactive T cells are multiplied in the lab to form an army, then infused back into the body to seek and destroy tumor cells.

Of the women in this trial, six were able to undergo the treatment, which also involved four doses of the checkpoint inhibitor Keytruda (pembrolizumab). That was given before the infusion, to keep the newly introduced T cells from being inactivated.

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Of those six patients, three saw their tumors shrink. One woman had a complete response, and remains cancer-free after more than 5.5 years. The other two patients had a partial response, then underwent surgery when some new tumor growth was found.

Both are now cancer-free 5 and 3.5 years, respectively, after receiving the immunotherapy.

“What we’re doing is creating a unique drug for each patient,” Rosenberg said. “That’s a new concept.”

Dr. Erica Mayer is an expert with the American Society of Clinical Oncology and an institute physician at the Dana-Farber Cancer Institute in Boston.

“These are very positive signals,” she said of the three patients’ outcomes.

Still, Mayer cautioned, much more remains to be learned about the immunotherapy’s effectiveness and long-term safety. Beyond that, she said, there will be questions about how to move such a complex treatment into the real world.

“Is this something that could be done outside of specialized centers?” Mayer said.

She also noted that various immunotherapy approaches are being studied for breast cancer, including combining immunotherapy drugs with other treatments, such as “targeted” medications.

“Our progress forward depends on ongoing clinical trials, and patients’ participation in them,” Mayer said.

More information

The U.S. National Cancer Institute has more on breast cancer treatment.

SOURCES: Steven Rosenberg, MD, chief, surgery branch, Center for Cancer Research, U.S. National Cancer Institute, Bethesda, Md.; Erica Mayer, MD, MPH, institute physician, Dana-Farber Cancer Institute, Boston, and volunteer expert, American Society of Clinical Oncology, Alexandria, Va.; Journal of Clinical Oncology, Feb. 1, 2022, online

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