New Antibody Treatment Slows Triple-Negative Breast Cancer Growth

Researchers at a leading cancer institute have developed an experimental antibody that shows early promise against triple-negative breast cancer, one of the most aggressive types. The treatment, tested in lab dishes and mice, targets a specific protein on cancer cells to deliver a toxin directly while waking up the body's immune defenses. These findings come from recent studies published in top medical journals, offering hope for patients with few good options.

Background

Triple-negative breast cancer makes up about 15 percent of all breast cancer cases. It lacks the receptors for estrogen, progesterone, and HER2 that doctors use to target other types. This means standard hormone therapies or drugs like Herceptin do not work. The cancer often grows fast, spreads early to places like the lungs and brain, and comes back even after initial treatment.

Patients with metastatic, or stage 4, triple-negative breast cancer face a five-year survival rate of just 12 percent. Current first-line treatments rely on chemotherapy combinations, but about half of patients do not live long enough to try second-line options. Doctors often pair chemo with immunotherapy drugs like pembrolizumab for tumors that test positive for PD-L1, a protein that helps cancer hide from immune cells. Even then, tumors progress quickly in many cases, with median progression-free survival around eight months.

Over the past five years, a drug called sacituzumab govitecan, sold as Trodelvy, has changed care for later stages. This antibody-drug conjugate, or ADC, locks onto a protein called TROP-2 on cancer cells and delivers a chemo toxin inside them. It is approved in over 50 countries for patients who have tried at least two prior treatments. More than 60,000 breast cancer patients have received it worldwide. Now, researchers aim to move such treatments earlier, to the first line, to help more people before their health worsens.

Key Details

The new antibody works in two main ways. First, it binds to TROP-2, a protein overexpressed on triple-negative cancer cells that drives their rapid growth. This binding lets the antibody sneak a powerful chemo drug right into the tumor cells, killing them from within. Lab tests showed it destroyed even cells that had grown resistant to standard chemotherapy.

Second, the antibody blocks signals that tumors use to shut down nearby immune cells. In triple-negative breast cancer, T-cells, the immune system's fighters, often get exhausted and stop attacking. After treatment, these T-cells perked up and started working again. This could make the body's own defenses stronger and pair well with immunotherapy drugs.

In mouse models, tumors grew much slower with the antibody. Some shrank completely. Lung metastases, a common deadly spread, dropped sharply. One study tracked tumors over weeks: treated mice had 70 percent less growth than untreated ones. The antibody also cleared out cancer cells that had spread to the lungs, something standard chemo often misses.

Clinical Trial Results

A large phase 3 trial called ASCENT-04/KEYNOTE-D19 tested sacituzumab govitecan combined with pembrolizumab in 400 patients with advanced, PD-L1-positive triple-negative breast cancer. After 14 months, the combo gave 11.2 months of progression-free survival, beating the 7.8 months from standard chemo plus pembrolizumab. Nearly 60 percent of patients responded, with responses lasting a median 16.6 months versus 9.2 months.

“There is a huge unmet need for new therapies for patients with triple-negative breast cancer,” said Sara Tolaney, chief of breast oncology at Dana-Farber Cancer Institute. “It is important that we work toward shifting these very effective novel drugs to the first line of therapy to move the needle and improve outcomes for these patients.”

The trial, published in the New England Journal of Medicine, involved sites across the U.S. and other countries. Results are headed to regulators for possible approval as first-line care. Pembrolizumab blocks PD-L1 to unleash immune attacks, and pairing it with the ADC seems to boost both targeted killing and immune response.

Other trials explore similar ADCs. One at UCSF tests sacituzumab tirumotecan alone or with pembrolizumab. Another combines avelumab immunotherapy with sacituzumab govitecan or other drugs for recurrent cases. TROP-2 targeting is expanding, with drugs like datopotamab deruxtecan in early tests.

What This Means

If approved for earlier use, this antibody combo could reach more patients right away. Right now, many deteriorate on first-line chemo and miss out on ADCs. Moving it upfront might extend lives and delay spread. For the 15 percent of breast cancer patients with triple-negative type, this offers a real shift after years of limited progress.

Doctors note side effects like low blood counts and diarrhea from ADCs, but they are often manageable compared to broad chemo. The combo builds on immunotherapy gains from trials like KEYNOTE-522, which added pembrolizumab to chemo for early-stage cases. In metastatic settings, it fills a gap where rapid progression leaves little time.

Researchers see ADCs as backbone therapies. They target TROP-2 found on most triple-negative tumors, unlike hormone-based options. Future studies may test them with other immunotherapies or in combinations for HER2-low cancers. Patient groups welcome the data, as black women and younger patients face higher rates of this subtype.

Ongoing work uncovers why some tumors resist. Not all respond to immunotherapy, so biomarkers like TROP-2 levels could guide who benefits most. This antibody revives exhausted T-cells, potentially widening immunotherapy's reach. For families hit by this disease, these steps mean fewer waits for second chances that may never come.