Key takeaways:
- A novel α-lactalbumin–targeting vaccine induced immune responses in 74% of participants in a phase 1 trial.
- The investigational vaccine demonstrated a favorable safety and tolerability profile across all study cohorts.
- Three distinct phase 1 cohorts included patients at high risk for recurrence, those with genetic risk factors, and patients receiving neoadjuvant therapy.
- Triple-negative breast cancer remains an aggressive subtype with higher prevalence among Black women, underscoring the need for preventive strategies.
- Phase 2 clinical trials are planned to further evaluate the vaccine’s effectiveness in preventing triple-negative breast cancer.
A novel vaccine for preventing triple-negative breast cancer has displayed a significant prevalence of immune response in phase 1 trials presented by Cleveland Clinic.1
Immune response was reported in 74% of study participants, alongside a positive safety and tolerability profile. This highlights progress toward developing treatment for triple-negative breast cancer, which is the most aggressive and lethal breast cancer subtype.
“The results from this trial are promising, as they suggest the investigational vaccine is not only safe and well tolerated but also capable of inducing immune responses in over 70% of participants,” said G. Thomas Budd, MD, lead study investigator from Cleveland Clinic’s Cancer Institute.
Study design and patient cohorts
The phase 1 clinical trial (NCT04674306) was conducted by Cleveland Clinic researchers to determine the safety and efficacy of the vaccine against triple-negative breast cancer. There were 35 patients included across 3 trial stages.
In phase 1a, there were 26 patients completing treatment for early-stage, triple-negative breast cancer within the past 3 years, currently tumor-free but with significant odds of recurrence. In phase 1b, there were 5 patients with genetic mutations linked to increased breast cancer risk agreeing to undergo a preventative mastectomy.
Finally, phase 1c included 5 patients with early-stage, triple-negative breast cancer undergoing preoperative chemoimmunotherapy and surgery, alongside being given pembrolizumab. Recurrence risk was identified in these patients by the presence of residual cancer in breast tissue.
Addressing an unmet need in triple-negative breast cancer
The trial was launched in 2021, addressing the significant need for triple-negative breast cancer treatment. The condition comprises 10% to 15% of breast cancer cases, with a 2-fold increase in prevalence among Black women and a high mortality rate. To prevent the condition, the vaccine targets α-lactalbumin, a lactation protein.
This protein is not present in normal aging breast tissues but has been observed in most triple-negative breast cancers. If these tumors develop, the immune system is stimulated by the vaccine to attack them.
The safety and efficacy of this method was originally proven in mouse models conducted by Vincent Tuohy, PhD, who was the Mort and Iris November Distinguished Chair in Innovative Breast Cancer Research at Cleveland Clinic. Tuohy’s research indicated significant benefits from activating the immune system.
Further development
To further develop these findings, investigators plan to evaluate the vaccine in a phase 2 clinical trial. The phase 1 findings were presented at the San Antonio Breast Cancer Symposium.
“Our findings that the majority of participants across all 3 cohorts demonstrated an immune response to α-lactalbumin is an encouraging sign for the vaccine’s potential moving forward,” said Julia Johnson, PhD, a researcher at the Cleveland Clinic.
Risk reduction strategies
This research marks a step toward preventing breast cancer. To further reduce risks, the American Medical Association published guidelines in June 2025.2 The guidelines recommend a plant-based diet, regular physical activity, moderation or avoidance of alcohol, and maintaining a healthy body weight.
Barnard also highlighted physical barriers in clinical settings, such as time constraints and reimbursement issues. To avoid these pitfalls, Barnard recommended referring patients to registered dietitians. Additionally, the “Let’s Beat Breast Cancer” campaign by the Physicians Committee for Responsible Medicine has taken steps to empower women and reduce breast cancer risk.
“An internist, or a surgeon, or an ob-gyn doesn’t have to become a nutrition and lifestyle coach,” said Barnard. “That’s what registered dietitians are for.”
