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Aims: Chemotherapy‐induced peripheral neuropathy (PN) is a treatment limiting toxicity of paclitaxel. We evaluated if EPHA genetic variation (EPHA4, EPHA5, EPHA6, and EPHA8) is associated with PN sensitivity by accounting for variability in systemic paclitaxel exposure (time above threshold). Methods: Germline DNA from 60 patients with breast cancer was sequenced. PN was measured using the 8‐item sensory subscale (CIPN8) of the patient‐reported CIPN20. Associations for 3 genetic models were tested by incorporating genetics into previously published PN prediction models integrating measured paclitaxel exposure and cumulative treatment. Significant associations were then tested for association with PN‐related treatment disruption. Results: EPHA5 rs7349683 (minor allele frequency = 0.32) was associated with increased PN sensitivity (β‐coefficient = 0.39, 95% confidence interval 0.11–0.67, p = 0.007). Setting a maximum tolerable threshold of CIPN8 = 30, optimal paclitaxel exposure target is shorter for rs7349683 homozygous (11.6 h) than heterozygous (12.6 h) or wild‐type (13.6 h) patients. Total number of missense variants (median = 0, range 0–2) was associated with decreased PN sensitivity (β‐coefficient: −0.42, 95% confidence interval −0.72 to −0.12, P =.006). No association with treatment disruption was detected for the total number of missense variants or rs7349683. Conclusion: Isolating toxicity sensitivity by accounting for exposure is a novel approach, and rs7349683 represents a promising marker for PN sensitivity that may be used to individualize paclitaxel treatment. [ABSTRACT FROM AUTHOR]

The enumeration of circulating tumor cells (CTCs) has shown prognostic importance in patients with breast cancer. However, CTCs are highly heterogeneous with diverse functional properties, which may also be clinically relevant. To provide a comprehensive landscape of the patient's disease, further CTC analysis is required. Here, a highly sensitive and reproducible graphene oxide based CTC assay is utilized to isolate and characterize CTCs from 47 metastatic breast cancer patients. The CTCs are captured with high purity, requiring only a few milliliters of blood and enabling efficient enumeration and subsequent analysis at both the protein and the transcription level. The results show that patient clinical outcomes correlate with the associated CTC profile and clearly demonstrate the potential use of the assay in the clinical setting. Collectively, these findings suggest that beyond simple enumeration, CTC characterization may provide further information that improves the diagnosis of the patients' disease status for proper treatment decisions. Moreover, this thorough validation study will facilitate the translation of the CTC assay into future clinical applications to broaden the utility of liquid biopsy. A graphene oxide based circulating tumor cell (CTC) assay is reported presenting high sensitivity and purity for isolating CTCs from metastatic breast cancer patients. Captured CTCs are characterized for their expression at both the protein and transcription level and correlated to clinical outcomes. The results demonstrate the potential use of the assay for future clinical applications broadening the utility of liquid biopsy. [ABSTRACT FROM AUTHOR]