Jerusalem, 15 November, 2026 (TPS-IL) — Israeli researchers have developed a blood test that can distinguish women with early-stage breast cancer from healthy women and identify patients at increased risk of recurrence. The test also detected molecular signs of aggressive cells in tumors otherwise classified as hormone-sensitive, offering new insight into why some breast cancers return.
Breast cancer is the world’s most commonly diagnosed cancer among women, with approximately 2.3 million new cases recorded worldwide in 2022. The development of more effective tools for detecting the disease and predicting its recurrence could therefore have significant implications for patient care.
The findings could eventually help doctors identify patients whose risk might be underestimated by conventional assessments and guide decisions about closer monitoring or additional treatment. The research also points to a potential new therapeutic approach: targeting chemical changes that affect how cancer cells function and may contribute to more aggressive behavior.
The study, published in the peer-reviewed journal Nature, was led by researchers from Israel’s Weizmann Institute of Science and the Hebrew University of Jerusalem.
Uncovering Aggressive Cancer Cells
The researchers focused on luminal breast cancer, one of the most common forms of the disease. Its cells typically carry receptors for hormones such as estrogen or progesterone, which can fuel their growth.
They analyzed 12 surgically removed, previously untreated breast tumors, most of them luminal tumors. Single-cell analysis revealed several distinct groups of cells, including a population with a basal-like profile. Basal-like breast cancers are generally associated with more aggressive disease.
These cells showed reduced hormone-receptor signaling and characteristics associated with cancer progression, including a greater ability to migrate in laboratory experiments. Their differences from other tumor cells were linked to epigenetic patterns – chemical modifications that affect how genes function without changing the underlying DNA sequence.
“The differences appear to be mainly epigenetic,” the Weizmann Insitute’s Prof. Efrat Shema said. She was referring to chemical changes that affect how genes are switched on or off without altering the DNA itself. In laboratory models, she explained, “an aggressive population always emerged eventually.”
To determine whether these patterns could also be detected in blood, the team adapted a technology called EPINUC. It analyzes cell-free nucleosomes – fragments of DNA wrapped around proteins and released when cells die. The method measures combinations of chemical marks on individual nucleosomes, along with selected proteins, using less than one milliliter of blood plasma.
In an initial group of 77 women with luminal breast cancer and 30 healthy women, the test successfully distinguished cancer samples from those of healthy participants.
The researchers then evaluated the technology using 188 samples from women with luminal breast cancer collected at multiple medical centers. A model trained on 75 percent of the data and tested on the remaining 25 percent achieved an area under the curve (AUC) of 0.96. A separate set of samples from the Mayo Clinic produced an AUC of 0.98.
The AUC measures how accurately a test distinguishes between two groups. A score of 1.0 represents perfect discrimination, while 0.5 indicates performance no better than chance.
The team also investigated whether the blood-based epigenetic patterns could help predict recurrence. In the Mayo Clinic group, which included five years of follow-up data, a model predicted relapse with an AUC of 0.81, outperforming models based on conventional factors such as cancer stage, tumor grade and subtype. In a smaller, separate group of patients, the test achieved an AUC of 0.92.
“When we looked for their epigenetic signature in blood samples, we found that the more prevalent it was, the greater the risk that the disease would come back,” Prof. Guy Ron of Hebrew University said.
The researchers stressed that further studies are needed to validate the findings and establish whether EPINUC can be used in clinical practice.