Genetic Insights in Taxane-Related Nerve Damage for Breast Cancer Survivors

Researchers have developed the first model for predicting the risk of nerve damage from taxane treatment in survivors of early-stage breast cancer (ESBC), according to the authors of a study published in Nature Precision Oncology. The findings could provide clinicians with alternative methods to identify and reduce the risk of prolonged complications and enhance individualization of treatment regimens for patients.

The predictive capabilities of these models show promise for reducing incidence and severity of TIPN in patients. Image Credit: © Pixel-Shot - stock.adobe.com

Due to advancements in early detection technology and treatment options, breast cancer (BC) is highly treatable when diagnosed in its early stages. Taxanes are a type of miotic inhibitor chemotherapy drug that blocks cell growth by interrupting cell division and is commonly used to treat ESBC, as well as advanced or metastatic BC. However, taxanes are associated with multiple adverse effects (AEs), including prolonged taxane-induced peripheral neuropathy (TIPN), which has significant quality of life implications. Risk factors such as advanced age, high body weight, and diabetes can increase the likelihood of developing peripheral neuropathy, but there has been no reliable method to identify which individuals have a higher risk.^1-3

The researchers surveyed AEs in 337 patients who had received either docetaxel (Docefrez; Sun Pharma Global) or paclitaxel (Taxol; Bristol Myers Squibb) who were between 2- and 6-years post-treatment. By sequencing the participants’ genes, they were able to build models that link genetic characteristics to known adverse effects of taxane therapy. The models tested for symptoms of numbness, tingling, cramps in feet, difficulty climbing stairs, and difficulty opening a jar. Cramps in the feet were the most common symptom reported by the participants.⁴

Based on whole-exome sequencing, 2 of the 5 prediction models—numbness in feet and tingling in feet—achieved area under the curve results above 60%. Using the model for numbness in feet, 73% of participants were correctly predicted (35 single nucleotide variants [SNVs]), while 70% were accurately predicted using the tingling in feet prediction model (55 SNVs). Both models included SNVs from the genes: ADAMTS20, APT6V0A2, CCDC88C, CYP2C8, EPHA5, NR1H3, PSKH2/APTV0D2, and SCN10A.⁴

“This can be a tool to individualize treatment, and not only to look at the benefits, but also to look at the risks for the individual patient,” said study author Kristina Engvall, MD, PhD, a doctor at the oncology clinic at Ryhov County Hospital in Jönköping, Sweden. “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.”⁵

The predictive capabilities of these models show promise for reducing incidence and severity of TIPN in patients, allowing for the identification of high-risk individuals to improve patient care. Additionally, the discovery of genetic characteristics that are associated to TIPN development opens avenues for further research and targeted interventions.

References

1. About Breast Cancer. American Cancer Society. Accessed July 15, 2024. https://www.cancer.org/cancer/types/breast-cancer/about.html

2. Taxane. National Cancer Institute. Accessed July 15, 2024. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/taxane

3. Taxol (paclitaxel): what to expect, side effects, and more. Breastcancer.org. March 9, 2024. Accessed July 15, 2024. https://www.breastcancer.org/drugs/taxol

4. Engvall K, Uvdal H, Björn N, et al. Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing. Precis Onc. May 16, 2024. doi:10.1038/s41698-024-00594-x

5. Nerve damage from breast cancer treatment can be predicted. News Release. July 9, 2024. Accessed July 15, 2024. https://www.eurekalert.org/news-releases/1050631