Originally published 2021-10-30.
In October 2021 Cleveland Clinic began testing an experimental vaccine designed to stop triple-negative breast cancer, the hardest form of the disease to treat, before it starts. The US Food and Drug Administration had cleared the Phase 1 study, which was funded by the US Department of Defense and run with the biotech company Anixa Biosciences. Final Phase 1 results, presented in December 2025, showed that the vaccine was safe and well tolerated and that about 74% of the 35 people who received it mounted an immune response.
That is encouraging, but it is not yet proof that the vaccine prevents cancer. Here is what the vaccine is, how it is meant to work, what the trial actually showed and what comes next.
What triple-negative breast cancer is
Doctors classify breast cancers partly by three markers on the tumour cells: receptors for the hormones oestrogen and progesterone, and a growth protein called HER2. Many breast cancers carry at least one of these, and that gives doctors a target. Hormone-blocking pills work against receptor-positive tumours, and HER2-targeted drugs work against HER2-positive ones.
Triple-negative breast cancer (TNBC) has none of the three. That means those targeted treatments do not work, and patients rely mainly on chemotherapy, surgery, radiotherapy and, in some cases, immunotherapy. According to Cleveland Clinic, citing the American Cancer Society, TNBC makes up roughly 10–15% of breast cancers but causes a disproportionately high share of breast cancer deaths. It is about twice as common in Black women, and 70–80% of breast tumours in people with inherited BRCA1 mutations are triple-negative.
For women at very high genetic risk, one of the main prevention options today is risk-reducing surgery to remove the breasts. A vaccine that could lower that risk without surgery would be a major change.
How the vaccine is meant to work
Most vaccines teach the immune system to recognise a germ. This one targets a protein made by the body itself: alpha-lactalbumin, a milk protein produced in the breast during breastfeeding.
The idea, developed over many years by Cleveland Clinic immunologist Vincent Tuohy, rests on a simple observation. Once a woman stops breastfeeding, healthy breast tissue stops making alpha-lactalbumin. Most triple-negative tumours, however, switch it back on. If the immune system can be trained to react to the protein, it should ignore normal ageing breast tissue but attack cancer cells that display it.
In mouse studies published in Nature Medicine, the approach prevented breast tumours from forming and slowed the growth of existing ones. That early research was partly paid for by donations from more than 20,000 people over 12 years. Tuohy, who died before the final human results were presented, described the method in 2021 as “a potential new way to control breast cancer.”
How the trial was set up
Phase 1 trials are the first step in human testing. Their job is to find a safe dose and check whether a treatment does what it is supposed to in the body, not to prove that it prevents or cures disease.
The study started with 18 to 24 planned volunteers who had finished treatment for early-stage TNBC within the past three years, were currently tumour-free and were at high risk of the cancer returning. Each received three vaccinations two weeks apart. Researchers began with low doses in a few people and increased the dose step by step, watching closely for side effects and immune responses. The original target completion date was September 2022, though the study ultimately ran much longer and grew to include more groups.
By the end, 35 people had taken part across three groups:
- Phase 1a (26 people): TNBC survivors at high risk of recurrence.
- Phase 1b (4 people): cancer-free people carrying high-risk genetic mutations who had chosen preventive mastectomy.
- Phase 1c (5 people): patients who still had some cancer in the breast after chemotherapy and immunotherapy before surgery, and who were receiving the immunotherapy drug pembrolizumab.
What the results showed
Cleveland Clinic presented the final Phase 1 results at the San Antonio Breast Cancer Symposium on 11 December 2025. The key findings were:
- Safety: the vaccine was well tolerated. The main side effect was mild skin inflammation where the injection was given.
- Dose: the team identified a maximum tolerated dose, the starting point for larger studies.
- Immune response: about 74% of participants developed an immune response against alpha-lactalbumin.
Principal investigator Dr G. Thomas Budd called the results promising, stressing that the vaccine was safe and triggered immune responses in more than 70% of participants.
What the results do not show yet
An immune response is a lab measurement: it shows that the body reacted to the vaccine. It does not tell us whether vaccinated people go on to develop fewer cancers. Answering that needs a much larger, longer trial comparing vaccinated people with similar people who did not receive the vaccine.
Anixa Biosciences, which holds the worldwide licence for the technology, has said it plans a Phase 2 study to test effectiveness, expected to start in late 2026 and run for about two to three years. Even if Phase 2 goes well, a Phase 3 trial and regulatory review would normally follow before any approval. Realistically, a licensed preventive vaccine is still years away.
Some early headlines called this a vaccine against breast cancer in general. That is not accurate. It targets a protein found mainly in triple-negative tumours, and so far it has been tested only in small groups of high-risk people.
Why researchers are watching closely
Most cancer vaccines in development are therapeutic: they are designed to help the immune system fight a cancer that already exists. A truly preventive cancer vaccine for healthy people would be rare. The best-known examples so far, the HPV and hepatitis B vaccines, work by preventing infections that can lead to cancer, rather than by targeting the tumour itself.
Tuohy’s research programme also explored the same strategy for other cancers linked to proteins that tissues stop making with age, including ovarian and endometrial cancer. If the breast cancer vaccine works, it could become a model for a new kind of cancer prevention.
What this means for you today
The vaccine is not available outside clinical trials. If you have a family history of breast or ovarian cancer, a known BRCA1 or BRCA2 mutation, or a past TNBC diagnosis, talk to a doctor or genetic counsellor about your personal risk, screening and prevention options, and about whether any clinical trials might suit you. Official trial registries list current studies and their eligibility rules.
Sources: Cleveland Clinic newsroom, 26 October 2021: Preventive breast cancer vaccine study launched; Cleveland Clinic newsroom, 11 December 2025: Final results of Phase 1 trial; earlier coverage by ScienceAlert.
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