LC–MS/MS-Based Profiling of Vitamin D Status as a Predictor of Paclitaxel-Induced Neuropathy in Breast Cancer Patients

Paclitaxel chemotherapy often causes nerve damage in patients, affecting up to 70% of those treated, with about 30% experiencing severe symptoms. While factors like age and genetics are known to influence risk, less is understood about adjustable factors such as low vitamin D levels. In response, a joint study conducted by researchers at Kafrelsheikh University and .Tanta University (both in Egypt) aimed to evaluate the association between pre-treatment vitamin D levels and the incidence of severe CIPN in breast cancer patients receiving paclitaxel-based chemotherapy. Pre-treatment vitamin D levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), A paper based on this research was published in Scientific Reports.¹

What is Paclitaxel and How Is It Used in Breast Cancer Treatment?

Paclitaxel is a commonly used and effective chemotherapy drug for treating several types of breast cancer, including hormone receptor-positive, HER2-positive, and triple-negative forms, and it is used in both early-stage and advanced disease. It works by interfering with the structures inside cancer cells that are needed for them to divide, effectively stopping the cells from multiplying. In patients with non-metastatic breast cancer, it is often given once a week for 12 weeks as part of combination treatment plans. Although this weekly schedule is generally better tolerated than less frequent higher-dose treatments, many patients still experience side effects that limit how much of the drug they can take, with nerve damage being one of the most serious and common problems.^2-4

Is Low Vitamin D Linked to a Higher Risk of Paclitaxel-Induced Nerve Damage in Breast Cancer Patients?

This study followed 300 breast cancer patients receiving paclitaxel chemotherapy over 12 weeks. Researchers measured vitamin D levels before treatment using blood tests and then tracked whether patients developed nerve damage during chemotherapy using a standard quality-of-life questionnaire focused on neuropathy symptoms. The research team found that about 39% of patients had low vitamin D levels before treatment. Those with low vitamin D were much more likely to develop severe nerve damage compared with patients who had sufficient levels. Patients who developed severe symptoms also tended to have lower vitamin D overall. Statistical analysis confirmed that low vitamin D was an independent risk factor for developing chemotherapy-induced nerve damage, even after accounting for other factors like age, body weight, and treatment differences.¹

“While causal inference cannot be drawn from this observational design,” write the authors of the paper,¹ “these findings provide a strong rationale for future randomized controlled trials to evaluate whether vitamin D supplementation could serve as a candidate preventive strategy to mitigate CIPN severity and optimize cancer therapy outcomes.”

In the opinion of the research team, future research should focus on whether vitamin D supplements can help prevent or reduce nerve damage caused by paclitaxel chemotherapy, ideally tested in well-designed clinical trials that ensure patients reach healthy vitamin D levels before treatment begins. Studies are also needed to understand how vitamin D may protect nerves at a biological level, including its effects on inflammation, oxidative stress, and nerve cell damage. In addition, researchers should explore whether genetic differences affect who benefits most from vitamin D and whether vitamin D levels influence how the drug behaves in the body. It will also be important to see if similar protective effects apply to other chemotherapy drugs that can damage nerves. Finally, longer-term data could help identify different patterns of nerve damage over time, and economic studies are needed to determine whether routine vitamin D testing and supplementation would be cost-effective in clinical practice.¹

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References

1. Elfeky, A. M.; El-Masry, M. I.; Mahmoud, A. A. et al. Pre-Treatment Vitamin D Insufficiency Predicts Severe Paclitaxel-Induced Sensory Neuropathy in Breast Cancer Patients: A Prospective Cohort Study. Sci Rep. 2026, 16 (1), 14282. DOI: 10.1038/s41598-026-50367-8
2. Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto, R.; Davies, C. et al. Comparisons Between Different Polychemotherapy Regimens for Early Breast Cancer: Meta-Analyses of Long-Term Outcome Among 100,000 Women in 123 Randomised trials. Lancet 2012, 379 (9814), 432-444. DOI: 10.1016/S0140-6736(11)61625-5
3. Sparano, J. A.; Wang, M.; Martino, S. et al. Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer. N Engl J Med. 2008, 358 (16), 1663-1671. DOI: 10.1056/NEJMoa0707056
4. Seidman, A. D.; Berry, D.; Cirrincione, C. et al. Randomized Phase III Trial of Weekly Compared with Every-3-Weeks Paclitaxel for Metastatic Breast Cancer, with Trastuzumab for All HER-2 Overexpressors and Random Assignment to Trastuzumab or Not in HER-2 Nonoverexpressors: Final Results of Cancer and Leukemia Group B Protocol 9840. J Clin Oncol. 2008, 26 (10),1642-1649. DOI: 10.1200/JCO.2007.11.6699