Triple-negative breast cancer vaccine shows promise in early clinical trial

When Chase Johnson was 31, his dog started acting strange. He was anxious, didn’t want to leave her, and one day he pushed his nose against her breast. Johnson felt a hard lump.

“I wasn’t someone who was good at doing self-exams, I don’t think I would have found it any other way,” said Johnson, now 36, of Cary, North Carolina. “I had no family history of breast cancer.”

Johnson was diagnosed with triple negative breast cancer in February 2021, an aggressive type of disease that tends to grow quickly and spread to other parts of the body.

Treatment of breast cancer depends in part on the presence of certain proteins on tumor cells, including estrogen and progesterone receptors, as well as a protein called HER2. Treatments can target these three proteins. Breast cancers that have no receptors and produce little or no HER2 are considered triple negative, making them more difficult to treat.

Johnson underwent four months of intravenous chemotherapy and surgery to remove her tumor and lymph nodes. After that, she underwent another six months of oral chemo and 24 cycles of radiation.

Her treatment was considered a success and she then began researching ways to prevent the cancer from recurring. About 40% of women with triple-negative breast cancer experience a recurrence during five years of treatment, and in about 30% of these women, the cancer recurs in the brain. It can also reappear in the lungs, liver and lymph nodes.

In December 2022, Johnson enrolled in an early-stage clinical trial at the Cleveland Clinic that is testing a new vaccine that researchers hope could stop recurrences of triple-negative breast cancer and, in some women, prevent the cancer from developing in the first place.

“I’m literally doing everything in my power to make sure this doesn’t happen again,” Johnson said. “For triple negative, resources are so limited; if traditional treatment methods don’t work, you’re just out of luck.”

The vaccine targets a protein called α-lactalbumin, present in about 70% of triple-negative breast cancers and found on the surface of tumor cells. If successful, the vaccine would teach the immune system to make T cells that attack and destroy cells containing the protein.

The latest results from the Phase 1 clinical trial, which included 35 women, were presented Thursday at the Breast Cancer Symposium in San Antonio, Texas.

The trial aimed to determine whether the vaccine was safe and whether it triggered an immune response in three groups of patients. (It did not examine how the vaccine affected outcomes.) The first group, which included Johnson, consisted of women who had recovered from early-stage triple-negative breast cancer and who did not have a tumor but were at high risk of recurrence. The second involved women who had undergone treatment for early-stage disease and had remaining tumor cells. The third group had not yet been diagnosed with breast cancer, but had a genetic predisposition, such as the BRCA gene, that put them at high risk for triple-negative cancer.

Researchers found that 74% of women developed an immune response to the vaccine – although it is still unclear what this result means for reducing recurrence or preventing disease.

“We don’t yet know whether this immune response will translate into reduced risk of recurrence or prevention of breast cancer,” said Dr. G. Thomas Budd, trial leader and a medical oncologist specializing in breast cancer at the Cancer Institute at the Cleveland Clinic.

The vaccine also appeared safe: Women reported redness or a lump at the injection site, but no serious side effects were observed.

One concern was whether the vaccine would trigger an autoimmune response, in which the immune system attacks the body by mistake. Women naturally produce α-lactalbumin when they breastfeed, which the vaccine could cause the body to attack. For this reason, Budd said he does not recommend women who want to breastfeed enroll in the trial.

The Phase 1 results, while promising, represent only a first step in determining whether the vaccine will prove effective.

A phase 2 trial is expected to begin late next year. This trial will be the first to determine whether the vaccine can reduce the risk of triple negative breast cancer coming back. If that goes well, future trials will test prevention in patients at genetic risk, Budd said.

Justin Balko, co-leader of the breast cancer research program at the Vanderbilt-Ingram Cancer Center, said the most promising use of the vaccine would be to prevent a first onset or recurrence of cancer, rather than targeting persistent cancer cells.

Indeed, over time, tumor cells can learn to hide target proteins from the immune system, Balko said. New cancer cells are less likely to develop this ability, he added.

Exploring a vaccine for triple-negative breast cancer is a welcome task, said Dr. Larry Norton, founding medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center in New York. The most effective targeted breast cancer treatments require the presence of estrogen receptors or HER2 in tumors.

“Triple negative doesn’t have either, so we’re left with just chemotherapy,” Norton said.

Even if the vaccine targeting α-lactalbumin is not effective in a phase 2 trial, Norton said scientists are getting better at identifying abnormal molecules found on different tumor cells. These abnormalities serve as targets for new therapies.

“There was a time when we would say HER2 is the worst type of breast cancer you could have, and then along came therapies targeting HER2 and now all of a sudden one of the worst prognostic markers becomes one of the best,” Norton said. “This could be the story of triple negative breast cancer if we find a target for it.”