Immune-based therapy shows promise against advanced breast cancer

WEDNESDAY, Feb. 9, 2022 (HealthDay News) — An experimental therapy that uses 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 study at the US 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 the patient’s immune system’s own T cells to target their genetically unique cancer.

At the moment, the team reports on only six women who have 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 has not yet been approved by the Food and Drug Administration,” emphasized senior researcher Dr. Steven Rosenberg, chief of surgery at 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 doesn’t legitimize much of an immune response — and is therefore usually not amenable to immunotherapy.

Immunotherapy refers to any treatment that turns on the immune system’s defenses to fight a disease. Several forms of cancer immunotherapy have already been approved, but not all cancers respond well to those drugs.

Melanoma is a good example of a cancer that responds well, Rosenberg said. Melanoma tumors carry many mutations, which can trigger a strong immune response. 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 little success to date in treating advanced breast cancer with available immunotherapies. Checkpoint inhibitors are approved for certain women with an aggressive breast cancer subtype known as triple negative.

The approach that Rosenberg’s team is developing is different. “We use the patient’s T cells as medicine,” 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.

In particular, 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, they can be amplified and used as a weapon.

The current study included 42 women with metastatic breast cancer who did not respond to conventional treatments. Metastatic means their cancer had spread. Each patient underwent surgery to remove a tumor sample, which the researchers genetically determined to identify the mutations.

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

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, is that tumors have tricks to evade the immune response. So those tumor-infiltrating T cells by themselves weren’t enough.

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

Of the women in this study, six were able to undergo the treatment, which also involved four doses of the checkpoint inhibitor Keytruda (pembrolizumab). This was given before the infusion to avoid inactivating the newly introduced T cells.

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 and then underwent surgery when new tumor growth was found.

Both are now cancer-free, respectively, 5 and 3.5 years after 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 at the American Society of Clinical Oncology and an institute physician at the Dana-Farber Cancer Institute in Boston.

“These are very positive signs,” she said of the three patients’ results.

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

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

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

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

More information

The US National Cancer Institute has more about breast cancer treatment.

SOURCES: Steven Rosenberg, MD, chief, division of surgery, Center for Cancer Research, US 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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