Triple Negative Breast Cancer Breakthroughs Signal New Hope

Triple-negative breast cancer (TNBC) has long stood out as one of the most challenging forms of cancer to treat, lacking the typical hormone or HER2 targets that make other breast cancers more responsive to established therapies. But in a flurry of recent research, scientists and clinicians are making headway on several promising fronts, from innovative vaccines to new drug combinations and even the discovery of novel molecular targets. The past year has seen a series of breakthroughs that could reshape the landscape for patients facing this aggressive disease.

At the 2025 San Antonio Breast Cancer Symposium, the Cleveland Clinic Cancer Institute presented results from a phase 1 clinical trial of an alpha-lactalbumin (aLA) vaccine, designed specifically for patients with TNBC or those at high risk for the disease. According to the Cleveland Clinic, the vaccine demonstrated an immune response in 74% of participants—a striking figure, given the notorious resistance of TNBC to most existing treatments. The study enrolled 35 patients who received three doses of the aLA vaccine, administered every two weeks. Blood samples were collected at set intervals to measure the immune system’s cellular and antibody responses.

The research builds on the pioneering work of the late Dr. Vincent Tuohy, who developed the "retired protein hypothesis." Dr. Tuohy discovered that aLA is over-expressed in about 70% of TNBC tumors and in the breast tissue of lactating women, but is otherwise largely absent from the body. This unique pattern made aLA an enticing target for immunotherapy. "Finding a candidate target to attack with the immune system is an exciting proposition," remarked Dr. G. Thomas Budd, a co-author of the study, highlighting the significant interest from both the patient and advocate communities.

The phase 1 trial established that a 10-microgram dose of the vaccine was safe and well-tolerated, with the only side effects being mild injection site reactions. As Dr. Budd explained, "We’ve demonstrated that giving this drug with immunotherapy and at least one type of chemotherapy can produce an immune response, and that the drug is tolerable." He added, "I foresee two potential paths forward. One is using the vaccine for patients with early triple-negative breast cancer who have operable disease and are receiving standard treatment but remain at risk for recurrence. The longer path and more promising one is using the vaccine to prevent triple-negative breast cancer. That’s a long-term goal on the horizon."

Based on these encouraging results, Anixa Biosciences, Inc. plans to launch a phase 2 trial of the vaccine in late 2026, with Cleveland Clinic supporting the design and patient enrollment. If the vaccine ultimately gains approval for preventive use, Dr. Budd noted that the first candidates would likely be individuals with BRCA1 or other high-risk genetic mutations. "As more people have access to multi-gene panels, hopefully we’ll be able to identify people at higher risk of developing cancer and one day offer preventative strategies like this vaccine to potentially take the place of prophylactic mastectomy," Dr. Budd said. While the road ahead remains long, the completion of the phase 1 study marks a major milestone in the quest for new TNBC treatments.

Meanwhile, another major advance was reported in the form of a phase 3 randomized controlled trial (ASCENT-04/KEYNOTE-D19), as detailed by 2 Minute Medicine. This international study enrolled 443 patients with previously untreated, PD-L1–positive, advanced TNBC across 28 countries. It compared the combination of sacituzumab govitecan (a Trop-2–directed antibody–drug conjugate) plus pembrolizumab (an immune checkpoint inhibitor) against the current standard of chemotherapy plus pembrolizumab.

The results were striking: patients receiving sacituzumab govitecan plus pembrolizumab experienced a median progression-free survival of 11.2 months, compared to 7.8 months in the chemotherapy group. The objective response rate was also higher in the experimental arm (60% versus 53%), and responses lasted longer—median 16.5 months versus 9.2 months. Importantly, the sacituzumab group had fewer treatment discontinuations due to toxicity (12% versus 31%), even though the rates of severe side effects were similar between the two arms. Diarrhea and neutropenia were common with sacituzumab govitecan, while chemotherapy was more often linked to anemia and neuropathy.

These findings suggest that sacituzumab govitecan, already used in later lines of TNBC treatment, may soon become a backbone therapy for patients with advanced, PD-L1–positive disease. The trial’s open-label design and immature overall survival data do leave some questions unanswered, but the improvement in progression-free survival and tolerability is a welcome development for patients and clinicians alike.

But the search for better TNBC therapies isn’t limited to new drugs or vaccines—it’s also happening at the molecular level. On January 28, 2026, a Purdue University research team led by Dr. Kyle Cottrell announced the discovery of a novel therapeutic target for TNBC: double-stranded RNA (dsRNA)-binding proteins, with a focus on a protein called PACT. As reported by USA TODAY, PACT acts to suppress another protein, RNA-activated protein kinase (PKR), which is involved in cellular antiviral responses and inflammation. The Purdue team found that TNBC cells are particularly sensitive to the depletion of PACT, suggesting that disrupting its function could be a promising strategy for treating this cancer subtype.

"Triple-negative breast cancer in particular seems to be quite sensitive to depletion of PACT, so it might be one of the better cancers to target for it. But there are definitely opportunities in other cancer types," Dr. Cottrell explained. PACT functions as a dimer—meaning two identical molecules join together to be active. The team’s research showed that if this dimerization is blocked, PACT can’t function, opening the door to new drugs that could inhibit this process. "We have to come up with some other way to prevent it from functioning. We found that PACT is a dimer. Two monomers of PACT come together, and if they don’t dimerize, then it can’t function. So, if you could block the dimerization, then you could inhibit its function in cells," Dr. Cottrell said. The next step will be to identify molecules that can prevent PACT dimerization, potentially leading to a brand-new class of TNBC therapies.

This research is part of Purdue’s One Health initiative and was supported by the National Institutes of Health and other organizations. It also highlights the growing importance of basic science in uncovering new therapeutic avenues for cancers that have stymied traditional approaches.

Altogether, these breakthroughs offer a glimmer of hope for patients with triple-negative breast cancer, a disease that for too long has been defined by its lack of options. From vaccines that rally the immune system to drug combinations that extend precious months of life, and now to the molecular mechanisms that keep cancer cells alive, researchers are finally making inroads against one of oncology’s toughest adversaries. While challenges remain and much work lies ahead, the momentum is undeniable—and for patients and their loved ones, that progress means everything.