Scientists identify genetic markers for common side-effect of taxane chemotherapy

In collaboration with Adfero

US scientists have identified genetic markers associated with a common side-effect of taxane-based chemotherapy called peripheral neuropathy.

Peripheral neuropathy is a condition of damaged nerves and affects about one-third of people taking taxane-based chemotherapy. It can result in numbness - and in some cases pain - in the legs and arms.

Certain people, such as older patients and those with a history of diabetes, are known to have an increased risk of neuropathy, but doctors are unable to accurately predict whether an individual will be affected.

Researchers at Indiana University hope that their latest discovery could lead to a blood test to determine whether a patient is likely to experience neuropathy if they are given taxane-based chemotherapy.

The research team identified the genetic markers by studying the genetic makeup of 2,204 breast cancer patients, all of whom took weekly paclitaxel for 12 weeks as part of a Phase III clinical trial and were then followed for a median of 15 months.

Analysis revealed that 613 patients had grade 2-4 neuropathy, while the other 1,591 patients were not affected.

The researchers looked for variations in DNA called single nucleotide polymorphisms (SNPs), which are single letter changes in the DNA sequence.

People with two 'normal' nucleotides in a specific gene called RWDD3 were found to have an average 27 per cent chance of developing neuropathy.

But patients with one normal nucleotide and one faulty version had a 40 per cent chance, while those with two faulty nucleotides had a 60 per cent chance of experiencing neuropathy while using taxane-based chemotherapy.

The researchers, whose findings were presented at the annual meeting of the American Society of Clinical Oncology, also found that older people and those from an African American background had a increased risk of neuropathy.

Lead author Dr Bryan Schneider, associate director of the Indiana Institute for Personalised Medicine, commented: "If these findings can be replicated, this may allow physicians to know prior to recommending therapy whether the patient is at an inordinate risk for developing taxane-induced neuropathy.

"This may allow for better counselling, use of alternative drugs or schedules, or omission of taxanes in the appropriate settings. These genetic findings might also provide insight into the mechanism of this side-effect and help develop drugs to prevent this toxicity altogether."

Dr Charles Swanton, head of translational research at Cancer Research UK's London Research Institute, said: "At the moment we don't know which patients will develop damage to the nervous system during taxane treatment for breast cancer. But this large, robust study takes us a step closer to developing a simple way to identify women most likely to experience this debilitating and sometimes painful side effect.

"These genetic markers could also be important clues to finding out how and why nervous system damage develops in the first place.

"Our work to identify genes that predict a woman's response to taxane therapy for breast cancer is closely related to this research. If these results are backed up by further research, such progress may help us to better tailor treatment to avoid this side effect."

References

  • Schneider, B.P. et al. Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103. J Clin Oncol 29: 2011 (suppl; abstr 1000)