Israeli blood test detects early breast cancer with 95% accuracy

An international team led by researchers at the Weizmann Institute of Science and the Hebrew University of Jerusalem has developed an experimental blood test that detects early-stage breast cancer with 95 percent accuracy for localized tumors under two centimeters (about 0.8 inches).

The test also outperforms conventional tissue biopsies in assessing the risk of recurrence after treatment.

The peer-reviewed study, published on Wednesday in the prestigious journal Nature, grew out of a collaboration between Dr. Efrat Shema’s lab at Weizmann, Hebrew University’s Prof. Guy Ron, and physicians at Kaplan Medical Center in Rehovot. Researchers in France, Germany, Italy, and the United States also participated in the research.

The scientists mapped breast tumors’ epigenetics, the unique molecular switches that control gene behavior, and discovered a particularly aggressive group of cells hiding among less harmful cancer cells.

“Breast cancer screening saves lives,” Shema said in a statement. “Regular mammograms reduce the risk of dying from the disease by 22 percent, but the denser the breast tissue, the easier it is for a tumor to ‘hide’ in the image.”

She noted that the newly developed blood test demonstrated strong diagnostic performance regardless of breast density.

Shema added that when the research expanded to evaluate blood samples from 188 patients with help from the Kaplan and Sheba medical centers, “it performed just as well across different types of breast cancer.”

Detecting epigenetic changes early

According to the World Health Organization, in 2022, roughly 2.3 million women were diagnosed with breast cancer worldwide, and 670,000 died.

The Israel Cancer Association reports that about 4,500 women are diagnosed with breast cancer in Israel each year, and about 900 die of the disease.

Currently, breast tumors are classified and treated based on their patterns of gene expression. But the epigenetic tags that govern those patterns have remained largely unmapped. In the new study, Dr. Noa Furth and Dr. Christina Riemenschneider of Shema’s lab, together with Yishai Arieli from Ron’s group, set out to decipher breast tumors’ epigenetic signatures.

Epigenetics refers to the chemical modifications that dictate which genes are turned on or off without altering the genetic code itself. These markers shift very early in cancer development and provide crucial information about cancer and where a tumor is taking root in the body.

To study these markers directly from patient tissue, speed is critical.

“We recruited 12 women who were scheduled to have their tumors surgically removed,” Furth said in a statement. “Once a tumor is removed, there’s only a short window of opportunity before its epigenetic tags begin to deteriorate. So, the doctors let me know as each surgery began. I rushed the tissue sample on ice from the hospital to our lab, and we started analyzing it that very day.”

Once the scientists mapped the primary tumor profiles, they sought to catch the same markers circulating in the blood. They focused on nucleosomes, the microscopic spool-like packages of DNA wound tightly around structural proteins that cells release when they break down.

A promising 2022 study co-authored by Ron and Shema already showed that blood tests could detect early-stage colorectal and pancreatic cancers.

This time, the team placed blood samples onto specialized glass slides and treated them with fluorescent antibodies engineered to recognize dozens of distinct chemical tags on these individual protein spools.

Using high-resolution, single-molecule fluorescence microscopy, the scientists’ imaging system scanned millions of these spools one by one.

Each tag was illuminated in a distinct color, creating a constellation of light that revealed the exact combination of active and inactive molecular switches. The physics group then used advanced computational algorithms and artificial intelligence to sift through millions of optical signals, isolating the coordinated pattern of a malignant tumor.

The scientists tested their new method on blood samples from 77 breast cancer patients who had been followed for at least five years at the Mayo Clinic in Florida, comparing them with samples from 30 healthy women. The trained artificial intelligence models distinguished between the two groups, achieving 95 percent accuracy in detecting early-stage breast cancer, when the tumor was still confined to the breast, measuring less than two centimeters.

Why does breast cancer recur?

Even when breast cancer is caught early, and treatment appears successful, the disease returns in 20 to 40 percent of cases.

This made the researchers wonder how cells with such different characteristics can coexist within the same tumor.

“The differences appear to be mainly epigenetic,” Shema explained. “When we grew breast cancer models in the lab starting with nonaggressive cells, an aggressive population always emerged eventually.”

These aggressive cells might be among the main culprits behind cancer recurrence. The scientists said that when they looked for this epigenetic signature in blood samples, they found that the more prevalent it was, the greater the risk of recurrence.

“Using this signature and additional epigenetic markers, we were able to distinguish with 81 percent accuracy between patients whose cancer returned during follow-up and those who didn’t experience a recurrence,” Ron said.

The test even flagged a risk of recurrence in patients considered low risk by conventional measures, the scientists said.

“Evidence is mounting that cancer cells exploit their epigenetic flexibility to change their behavior, becoming more aggressive, and evading treatment,” Shema said.

Shema, whose research is supported by the Swiss Society Institute for Cancer Prevention Research and by Spain’s Fundación Alberto Palatchi, noted that the findings could open new avenues for therapy by tracking aggressive cell populations in different types of cancer.

“In the future, they could help us not only predict recurrence but also search for ways to prevent it,” Shema said. “We’re now looking for treatments that could deprive cancer cells of their epigenetic flexibility — and perhaps even coax cells that have already turned aggressive into adopting less aggressive traits.”