Header Image by National Cancer Institute on Unsplash.
As many as one in eight women worldwide will develop breast cancer in her lifetime. For 30% of these women, the disease will reach the incurable metastatic stage, where cancer cells spread to distant organs. At this stage, the tumor becomes highly heterogeneous, like a chameleon changing its colors. This allows it to adapt to ongoing therapy and eventually become resistant, until patients are left with no more treatment options.
The adult human body is about 60% fluid by weight, but blood only makes up about 7-8% of this. There are many other types of liquids, including saliva, urine, cerebrospinal fluid around the brain and spine, and pleural fluid around the lungs.
Liquid biopsy is a method that has extensively been used to non-invasively detect and characterize cancers, by analyzing tumor components like DNA fragments in circulation in our body. However, liquid biopsies have so far mainly been carried out in blood, not in other fluids. It was unclear if all metastatic cancer sites contribute equally to the tumor information present in the blood, and whether non-blood fluids convey the same information.
Blood and non-blood fluids that we collect in our research. Created in BioRender. Richard, F. (2025)
Cancer Detection in Non-Blood Fluids
To answer these questions, we’ve conducted a study at the Laboratory for Translational Breast Cancer Research in KU Leuven as part of the UPTIDER program, where we compared tumor information from metastatic sites and body liquids in patients with metastatic breast cancer. To evaluate how metastatic sites were reflected in the different liquids we used phylogenetic reconstruction. This method is like creating a family tree: it shows how different samples of cancer cells are related by comparing their genetic information, allowing us to estimate how similar or different two samples are to each other.
What we found was that tumor information in different in each body liquid. This means that metastatic sites are not equally represented in all body liquids, with brain metastases being better represented in the cerebrospinal fluid than in blood, for example. It also appears that certain metastases, such as the ones in the lungs, are not well represented in any liquids. Importantly, in 40% of the patients, the tumor could not be detected in the blood, but it could be detected in other body fluids.
“In 40% of the patients, the tumor could not be detected in the blood, but it could be detected in other body fluids.” – François Richard, KU Leuven
Opening Doors to New Treatment Options
These results are vital, because in clinics today, patients are only eligible for many new targeted treatments if specific cancer information is found in a liquid biopsy from the blood. For example, two cancer drugs called alpelisib or inavolisib inhibit specific proteins that help cancer cells grow and survive — but they are currently only given to patients if a mutation in the PIK3CA gene is found in their blood.
Because our research showed that this mutation could go undetected in blood but still be present in another liquid in the body, this work opens the possibility of more patients benefiting from specific cancer drugs, if multi-source liquid biopsies are used when screening for suitable treatments.
“This work opens the possibility of more patients benefiting from specific cancer drugs, if multi-source liquid biopsies are used when screening for suitable treatments.” – François Richard, KU Leuven
UPTIDER: A Unique Tissue Donation Program
This research relies on UPTIDER (UZ/KU Leuven Program for Tissue Donation to Enhance Research) — a unique, worldwide postmortem tissue donation program. In UPTIDER, patients with metastatic breast cancer that unfortunately died from their disease undergo an autopsy. It is performed rapidly after death, and all body liquids and metastatic sites are sampled. The body is then quickly given back to the family.
This program brings together medical doctors, pathologists, bioinformaticians, technicians and researchers to work within a robust open science environment. The program tracks clinical and sample data, ensuring that everyone has access to the most up-to-date information. It also facilitates effective collaboration and ensures compliance with regulations, from patient inclusion to publication. This infrastructure allows us to transform the trust placed in us by patients and their families into impactful research and hope for future patients.
“This infrastructure allows us to transform the trust placed in us by patients and their families into impactful research and hope for future patients.” – François Richard, KU Leuven
Our work suggests that a multi-source liquid biopsy approach could open new treatment opportunities for patients, especially by unveiling tumor information missed in blood but found in non-blood fluids. We need to confirm these findings in future clinical trials including blood and non-blood liquid biopsies. We can also extend our investigation to other metastatic cancer types, in addition to breast cancer.
In all, our work provides a seed of hope for better detection and treatment options for more cancer patients in the future.
Written by François Richard for the SciMingo Popular Science Writing Course.
