Many women treated for breast cancer with taxanes, a type of cytostatic drug, often experience side effects in the nervous system. LiU researchers have developed a tool that can predict the level of risk for each individual. This tool could help doctors tailor treatment to avoid persistent side effects in those at greatest risk.
Some people experience serious side effects from cancer treatment, while others manage it without major complications. Henrik Gréen’s research group wants to find ways to predict the risk of serious side effects. Image credit: Magnus Johansson/Linköping University
More and more people are surviving cancer. But even if they have survived the disease, a growing number of people still suffer from the side effects of cancer treatment. In a recent study from Linköping University, researchers investigated the side effects of taxanes, a chemotherapy drug used to prevent breast cancer from recurring. The downside of the treatment is that some patients suffer nerve damage as a side effect.
“Side effects in the form of nerve damage are very common after taxane treatment for breast cancer, and they often persist for several years. For those affected, it is extremely stressful and has a major impact on quality of life. It is therefore a major clinical problem, which has received more attention in recent years, but there is no way of knowing which people are most at risk of side effects,” says Kristina Engvall, who recently completed her PhD at Linköping University and is a physician at the Oncology Clinic at Ryhov County Hospital in Jönköping.
Cramps, numbness and tingling
The researchers began by looking closely at side effects in patients treated for breast cancer with docetaxel or paclitaxel, the two most common taxanes. Between two and six years had passed since treatment. The 337 patients were asked to describe the severity of nerve damage they suffered, or peripheral neuropathy, as it is also known. Foot cramps were the most common, affecting more than one in four patients. Other side effects included difficulty opening a jar, numbness in the feet, tingling in the feet and difficulty climbing stairs.
The researchers sequenced the patients’ genes and then built models linking the genetic characteristics to various side effects of taxane treatment. This allows the models to predict the risk of nerve damage. This type of model, called a prediction model, did not previously exist for taxane-induced peripheral neuropathy. The researchers were able to model the risk of persistent numbness and tingling in the feet.
A growing patient group
Both models were able to separate patients into two clinically relevant groups: one with a high risk of persistent side effects and one that matched the frequency of peripheral neuropathies in the normal population. The researchers used two-thirds of the data to train the models using machine learning. They were then able to use the remaining third of patients to validate the models, which proved very effective. Validating that the models also work in a different group is an important step.
“This is the first time that a prediction model has been developed that can predict the risk of nerve damage related to taxane treatment. Women who have been treated with taxanes after breast cancer surgery are a very important group in healthcare worldwide. This is therefore a major and clinically relevant problem,” says Henrik Gréen, professor at Linköping University, who led the study published in the journal npj precision oncology.
Weighing the benefits versus the risks
“It can be a tool to individualize treatment, and not only to look at the benefits, but also to look at the risks for each patient. Today, we are so good at treating breast cancer that we need to focus more on the risk of complications and side effects that affect the patient long after treatment,” says Kristina Engvall.
In the long term, the prediction model could be adopted as routine in healthcare. But first, research is needed to determine whether the prediction model also works well in other population groups than the Swedish population.
“It also turned out that three of the five symptoms we focused on are so biologically complex that we cannot model them. These include, for example, difficulty opening cans. Opening a can involves both motor and sensory nerves, making it very difficult to predict which individuals are most at risk of developing this symptom,” says Henrik Gréen.
The study was funded with support from, among others, the Swedish Cancer Society, ALF funding, the Medical Research Council of South-Eastern Sweden (FORSS) and Futurum in the Jönköping Region.
The article: Prediction models for taxane-induced persistent peripheral neuropathy in breast cancer survivors using whole-exome sequencingKristina Engvall, Hanna Uvdal, Niclas Björn, Elisabeth Åvall-Lundqvist and Henrik Gréen, Precision Oncology npjPublished online May 16, 2024, doi: https://doi.org/10.1038/s41698-024-00594-x
Written by Karin Söderlund Leifler
Source: Linköping University
Originally published in The European Times.
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