Researchers in Israel have developed a liquid biopsy that detects early-stage breast cancer with 95 percent accuracy while identifying patients at high risk of recurrence.
The test, detailed in a study published on November 11, 2026, in Nature, analyzes chemical tags on proteins wrapping DNA in the bloodstream.
The study was spearheaded by Professor Guy Ron of the Hebrew University of Jerusalem and Professor Efrat Shema of the Weizmann Institute of Science, with the objective of clarifying why hormone receptor-positive breast tumors can contain basal-like cancer cells that are epigenetically unique and exhibit aggressive biological traits.
The research, titled Epigenetic Heterogeneity in Breast Tumours Informs Diagnosis and Prognosis, was conducted by an international group of investigators including Dr. Noa Furth, Christina Riemenschneider, Yishai Arieli, and Guy Ron alongside Efrat Shema. Christina Riemenschneider from Shema’s laboratory worked in cooperation with Yishai Arieli from Ron’s research group to decipher the epigenetic signature of breast cancer tumors.
Fluorescent labeling of multiple different epigenetic tags and single-molecule microscopy form the foundation of the new blood test. By connecting these concealed cellular groups to circulating nucleosome signatures, the investigators also show the capability of a blood-based test to spot breast cancer and gauge recurrence likelihood.
The findings offer a new perspective on intratumoral heterogeneity, although prospective validation is required before clinical application. Pinpointing the chromatin traits that set basal-like cells apart from luminal cells served as a primary goal of the research.
The investigators found consistent differences in multiple histone modifications. Basal-like cells exhibited increased H3K9me2, H3K4me1, and H3K4me3. In contrast, luminal cells showed greater enrichment of modifications including H4K20me3, H3K36me3, H3K9me3, and H3K27me3. These patterns indicated that cellular identity was associated with coordinated differences in chromatin organization.
“By detecting signals in the blood, researchers are exploring whether they can identify breast cancer and which tumors carry a higher risk of recurrence,” said Dr. Lucy Hooper, general practitioner and co-founder of Coyne Medical.
Researchers Map Epigenetic Markers Across Millions of Nucleosomes
Using single-molecule microscopy and fluorescent labels, the researchers mapped dozens of epigenetic markers across millions of nucleosomes.
Ron’s team applied computational tools to identify patterns associated with cancer and the risk of recurrence. Those early tumors measured no more than two centimeters and were localized. The diagnostic performance remained strong regardless of breast density, addressing a key limitation of standard mammography.
The research team expanded their evaluation to 188 patient blood samples with assistance from Sheba Medical Center and Kaplan Medical Center, confirming that the assay maintained its performance across different breast cancer types.
Detecting Hidden Aggressive Cells
To capture tissue samples before fragile epigenetic tags deteriorated, researchers maintained a rapid-transport protocol. Furth reported that the team recruited 12 patients who were scheduled to undergo tumor removal surgery. Collection and analyses of breast cancer tissue samples and matching blood samples were approved by the Israeli Ministry of Health Ethics Committees under Helsinki applications KMC-0028-22, followed by approval of the Weizmann Institutional Review Board under IRB reference 2314-3.
Breast cancer samples for histone PTM mass-spectrometry-based analysis comprised 21 tumours obtained from patients undergoing surgery at the European Institute of Oncology as part of a study approved by the institute’s Ethical Committee under study UID 2550.
Mayo Clinic provided data and plasma samples for luminal breast cancer patients under IRB approval number 23-011311, whereas the Institutional Review Board authorized the collection of plasma samples from breast cancer patients treated at Sheba Medical Center under IRB approval 7509-09.
“Once the tumor is removed, there is only a narrow window of time during which the epigenetic tags remain intact. So whenever a surgery began, the doctors called me. I quickly transported the biopsy sample on ice from the hospital to the laboratory, and we began analyzing it that same day,” Furth explained, according to All Israel News.
When the scientists searched patient blood samples for the specific epigenetic signature of those aggressive cells, higher levels correlated directly with an increased likelihood of recurrence.
“When we searched the blood samples for the epigenetic signature of the aggressive cell population we had identified in the tumors, we found that the more prevalent this signature was, the greater the risk of the disease returning,” Ron said.
Combining that aggressive signature with other epigenetic markers allowed researchers to distinguish between patients who experienced a recurrence and those who remained disease-free with 81 percent accuracy.
“Evidence is mounting that cancer cells exploit their epigenetic flexibility to change their behavior, become more aggressive and evade treatment,” Professor Efrat Shema, one of the study's authors, said.
Readers should consult qualified healthcare professionals regarding medical concerns, as these findings represent an experimental study requiring further clinical validation before routine implementation.
Earlier coverage: Two Common Forever Chemicals Linked to Aggressive Breast Cancer Subtype