A multi-dimensional framework for predicting taxane-induced peripheral neuropathy in Black women with breast cancer: findings from ECOG-ACRIN EAZ171

Résumé fourni par la source

Taxane-induced peripheral neuropathy (TIPN) is a critical drug-related toxicity impacting many breast cancer patients. EAZ171 previously found that for patients of Black race, every three-week docetaxel had less TIPN compared with weekly paclitaxel. Here we set out to determine whether clinical, social, and genetic variables could further refine the risk in EAZ171. We found that single marital status ( p value = 0.018) decreased risk, whereas paclitaxel ( p value = 0.002), higher BMI ( p value = 0.037), poor physical functioning ( p value = 0.04), and lower emotional well-being ( p value = 0.01) increased risk of TIPN. A germline variant in FCAMR (rs1578279) was the top association in a GWAS meta-analysis across E5103 and EAZ171 ( p value = 4.9 ×10 -8 ). Deleterious rare germline variants in SBF2 were associated with increased risk in a combined E5103/EAZ171 WES analysis ( p value = 0.03). This work demonstrates that the risk of TIPN in Black patients with breast cancer can be better risk stratified, and possibly modified when considering key clinical, social, and genetic variables.

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