Update: Breast cancer vaccine trial begins enrolling people with BRCA1 and PALB2 mutations

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Research Timeline: Human Research

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What is this update about?

Scientists have been working for years to develop a vaccine that will prevent breast cancer. A small, early-phase study has begun to test whether this new vaccine is safe and effective in humans.

Why is this update important?

Initially, this trial was open only to people with non-metastatic triple-negative breast cancer (TNBC) to see if the vaccine could prevent a recurrence. We published an XRAY review on the press release about the opening of the study. However, the trial has recently expanded to include people who do not have breast cancer but who are at high risk of developing TNBC due to an inherited mutation in BRCA1 or PALB2.

This next phase of the study will allow researchers to determine if the vaccine can lower the risk for breast cancer in people who are high risk but have not been diagnosed with the disease.

Breast cancer vaccine trial eligibility

Initially, the trial only included those with TNBC (phase 1a). The trial now has opened to people at high risk of developing TNBC due to an inherited mutation (phase 1b). Both versions of the trial are currently recruiting participants.

• Phase 1a (the TNBC group) is recruiting people diagnosed with TNBC who have:
  • stage 2-3 TNBC.
  • completed all standard therapy.
  • no evidence of recurrence within 3 years after diagnosis.
• Phase 1b (the prevention group) is recruiting people who:
  • are at high risk of developing breast cancer due to an inherited mutation in BRCA1 or PALB2 and are planning to have a prophylactic bilateral mastectomy.
  • have no evidence of breast cancer.

Phases 1a and 1b will test not only the safety of the vaccine but also its effectiveness in preventing breast cancer. Phase 1a will test whether the vaccine can decrease recurrence in people who have been diagnosed with non-metastatic TNBC. Phase 1b will test how well the vaccine prevents breast cancer in high-risk people (BRCA1 and PALB2 mutation carriers) who have not had the disease.

This trial is being conducted at the Cleveland Clinic in Cleveland, Ohio. More information can be found here. A third arm of the study, which is not yet enrolling participants, will test the vaccine in people with TNBC who are being treated with the checkpoint inhibitor pembrolizumab.

What does the vaccine do?

The vaccine trains the immune system to kill cells that make a substanced called "alpha-lactalbumin," a protein that appears on breast cells late in pregnancy and during breastfeeding. Once a woman is no longer pregnant or breastfeeding the protein is no longer made. However, women who develop breast cancer, particularly TNBC, also produce alpha-lactalbumin on their breast cancer cells.

The development of this vaccine is based on more than 10 years of research. In 2010, researchers published study results showing that the vaccine dramatically decreased breast cancer in mice. Importantly, this study also found that the vaccine did not cause inflammation in normal non-breast tissue. In 2016, tests on lab-grown human breast cancer cells, breast tumor samples and breast tumors in mice showed that the vaccine has the potential to be safe and effective.

Like most phase I trials that test safety, this trial is small. Phase 1a will include up to 30 people with non-metastatic TNBC who are at high risk of recurrence. The number of people who will be enrolled in Phase 1b has not been posted yet on clinicaltrials.gov.

What does this mean for me?

This research is early and scientists cannot yet tell how well the vaccine prevents cancer. However, if you have a BRCA1 or PALB2 inherited mutation, have never been diagnosed with cancer and are planning a risk-reducing mastectomy, you may qualify for this study.

You may also qualify for participation if you have been diagnosed with stage 2 or stage 3 triple-negative breast cancer and you have a high risk of your cancer returning.

Currently, the study is enrolling patients only in Cleveland, Ohio, so participants outside of the area would need to travel to participate. As this research continues, participation may be expanded to more cancer centers. If you are interested in participating, speak with your doctor and contact the study team listed on clinicaltrials.gov to see if you qualify for enrollment.

It is not known whether or when this vaccine might be available to the public. Even if the research is successful, availability will likely take several years. If the vaccine proves to be effective and is approved for breast cancer prevention, people who are breastfeeding or plan to breastfeed in the future would not be eligible to receive it.

Reference

Budd G, Johnson JM, Rhoades E, et al. Phase I trial of an alpha-lactalbumin vaccine in patients with operable triple-negative breast cancer (TNBC). Poster OT2-10-02 presented at the San Antonio Breast Cancer Symposium, December 6-10, 2022.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 1/9/23