One of the great hopes of cancer medicine over the past decade has been a simple blood test that would detect cancer at its earliest stages, help physicians choose the right treatment and even predict the risk of recurrence. Known as liquid biopsies, these tests work by identifying traces of cancer cells in the bloodstream. Although they are already used to tailor treatment for some patients, they still struggle to detect cancer early in the general population or predict whether the disease will return after treatment. One reason is that, in the early stages, genetic traces of cancer in the blood are extremely scarce and hard to detect without triggering false alarms – results suggesting cancer when none is present.
Now researchers from the laboratories of Prof. Guy Ron at the Hebrew University of Jerusalem and Prof. Efrat Shema at the Weizmann Institute of Science have developed a blood test that distinguishes with high accuracy between women with early-stage breast cancer and healthy women.
The test also outperforms conventional tissue biopsies in predicting the risk of recurrence after treatment.
The findings, published in Nature, grew out of a collaboration with physicians at Kaplan Medical Center in Rehovot. Together, the researchers decoded the distinctive epigenetic signatures of breast tumors and identified a particularly aggressive population of cells lurking within them.
If DNA is the cookbook that every cell in the body keeps on its shelf, epigenetic tags are the sticky notes and bookmarks telling the cell which recipes to follow and how often to use them. In cancer cells, things can go wrong both with the recipes themselves, through genetic mutations, and with the instructions for using them. Although breast tumors are already classified and treated according to their patterns of gene expression, the epigenetic tags that help control these patterns have yet to be fully mapped. 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 the epigenetic signatures of breast tumors.
“We recruited 12 women who were scheduled to have their tumors surgically removed,” Furth recalls. “Once a tumor is removed, there’s only a short window before its epigenetic tags begin to deteriorate. So whenever surgery began, the doctors would alert me. I would rush the tissue sample from the hospital to our lab on ice, and we’d start analyzing it that very day.”
Having mapped the epigenetic signatures of breast tumors from several women, the scientists looked for a way to detect those signatures in blood, to enable early diagnosis. They built on a technology developed by Shema that takes advantage of a natural process: When cells die, including cancer cells, they release nucleosomes – segments of DNA wrapped around proteins – into the bloodstream.
Using single-molecule microscopy and fluorescent labels that recognize dozens of different epigenetic tags, the technology can map epigenetic changes in millions of nucleosomes. In fact, in a 2022 study, it had already shown promise for detecting colorectal and pancreatic cancers at an early stage through a blood test.
Importantly, collecting all these molecular measurements was only half the challenge. The researchers also needed to find the telltale patterns hidden in this wealth of data. That’s where Shema’s expertise in epigenetics and single-molecule technologies met the quantitative approach of Ron’s physics group. The latter approached the challenge like an experimental physics problem, using computational analysis to identify patterns that could help detect cancer and predict its return.
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, along with samples from 30 healthy women. They trained artificial intelligence models to distinguish between the two groups, achieving 95 percent accuracy in detecting early-stage breast cancer, when the tumor was still confined to the breast and measured no more than two centimeters.
“Breast cancer screening saves lives,” Shema says. “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. Our blood test showed strong diagnostic performance regardless of breast density. It performed just as well across different types of breast cancer, and also when we expanded the number of patient blood samples to 188 with the help of Sheba and Kaplan medical centers.”
Now researchers from the laboratories of Prof. Guy Ron at the Hebrew University of Jerusalem and Prof. Efrat Shema at the Weizmann Institute of Science have developed a blood test that distinguishes with high accuracy between women with early-stage breast cancer and healthy women.
The test also outperforms conventional tissue biopsies in predicting the risk of recurrence after treatment.
The findings, published in Nature, grew out of a collaboration with physicians at Kaplan Medical Center in Rehovot. Together, the researchers decoded the distinctive epigenetic signatures of breast tumors and identified a particularly aggressive population of cells lurking within them.
If DNA is the cookbook that every cell in the body keeps on its shelf, epigenetic tags are the sticky notes and bookmarks telling the cell which recipes to follow and how often to use them. In cancer cells, things can go wrong both with the recipes themselves, through genetic mutations, and with the instructions for using them. Although breast tumors are already classified and treated according to their patterns of gene expression, the epigenetic tags that help control these patterns have yet to be fully mapped. 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 the epigenetic signatures of breast tumors.
“We recruited 12 women who were scheduled to have their tumors surgically removed,” Furth recalls. “Once a tumor is removed, there’s only a short window before its epigenetic tags begin to deteriorate. So whenever surgery began, the doctors would alert me. I would rush the tissue sample from the hospital to our lab on ice, and we’d start analyzing it that very day.”
Having mapped the epigenetic signatures of breast tumors from several women, the scientists looked for a way to detect those signatures in blood, to enable early diagnosis. They built on a technology developed by Shema that takes advantage of a natural process: When cells die, including cancer cells, they release nucleosomes – segments of DNA wrapped around proteins – into the bloodstream.
Using single-molecule microscopy and fluorescent labels that recognize dozens of different epigenetic tags, the technology can map epigenetic changes in millions of nucleosomes. In fact, in a 2022 study, it had already shown promise for detecting colorectal and pancreatic cancers at an early stage through a blood test.
Importantly, collecting all these molecular measurements was only half the challenge. The researchers also needed to find the telltale patterns hidden in this wealth of data. That’s where Shema’s expertise in epigenetics and single-molecule technologies met the quantitative approach of Ron’s physics group. The latter approached the challenge like an experimental physics problem, using computational analysis to identify patterns that could help detect cancer and predict its return.
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, along with samples from 30 healthy women. They trained artificial intelligence models to distinguish between the two groups, achieving 95 percent accuracy in detecting early-stage breast cancer, when the tumor was still confined to the breast and measured no more than two centimeters.
“Breast cancer screening saves lives,” Shema says. “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. Our blood test showed strong diagnostic performance regardless of breast density. It performed just as well across different types of breast cancer, and also when we expanded the number of patient blood samples to 188 with the help of Sheba and Kaplan medical centers.”
