Assessing association of heavy metal levels in urine and sera with neurotoxicity in breast cancer(BC) patients undergoing adjuvant/neoadjuvant chemotherapy.

Abstract

e12510 Background: Standard adjuvant chemotherapy for early stage BC includes taxane therapy with paclitaxel or docetaxel. Taxanes are associated with peripheral neuropathy in some patients, which can impact appropriate dosing and quality of life. In this study, we investigated whether there is an association between the levels of heavy metals in serum or urine and the development of high-grade peripheral neuropathy, defined as grade ≥2 (utilizing CTCAE v.4.0) in a cohort of BC patients undergoing neo/adjuvant taxane chemotherapy. Methods: BC patients undergoing treatment with taxanes were identified in the clinic. Patient eligibility included: histologically confirmed invasive mammary carcinoma, Stage I-III BC, undergoing neo/adjuvant treatment with taxane chemotherapy. Patients previously treated with chemotherapy or who had pre-existing neuropathy were not eligible. Patients were consented and prior to study enrollment, study participants provided blood and urine samples to assess for heavy metals. Neurotoxicity was measured using the NCI CTCAE v.4 criteria throughout patient’s taxane treatment. Serum and urine samples collected at baseline were analyzed for heavy metals by inductively coupled plasma mass spectrometry (ICP-MS). Results: 115 female patients were enrolled. 111 patients were included in the analysis; 4 patients were excluded due to withdrawal from study prior to receiving any taxane treatment. Participants were 78% White (6% of Hispanic origin), 19% Black and 3% Asian with an average age of 51 years (range 26-72). ICP-MS was used for the analysis of Aluminum (Al), Manganese (Mn), Cobalt (Cu), Zinc (Zn), Arsenic (As), Cadmium (Cd), Mercury (Hg), Thallium (Tl), and Lead (Pb) levels in patients’ serum and urine. Patients with neurotoxicity grade >=2 had significantly lower serum Arsenic levels (mean=0.37 [SD=1.08], n=89] than subjects with toxicity grades 0-1 [mean=1.21 (SD=2.33), n=22] (p=0.037; Wilcoxon test). Other than Arsenic no relationship of the other heavy metals and neurotoxicity was found in the serum. We did not observe significant associations between heavy metal levels in urine and neurotoxicity grade. Conclusions: Taxane treatment is an effective BC therapy but its utility is limited by its associated toxicity of peripheral neuropathy. The source of the higher arsenic levels is unclear. We conclude that there is no evidence that high levels of heavy metals were associated with taxane induced neurotoxicity in our study.