Abstract
Copper plays a key role in cancer metastasis, which is the most common cause of cancer death. Copper depletion treatment with tetrathiomolybdate (TM) improved disease-free survival in breast cancer patients with high risk of recurrence in a phase II clinical trial. Because the copper metallochaperone ATOX1 was recently reported to drive breast cancer cell migration and breast cancer migration is a critical factor in metastasis, we tested if ATOX1 expression levels in primary tumor tissue could predict the TM treatment outcome of breast cancer patients at high risk of recurrence. We performed ATOX1 immunohistochemical staining of breast tumor material (before TM treatment) of 47 patients enrolled in the phase II TM clinical trial and evaluated ATOX1 expression levels in relation with patient outcome after TM treatment. Our results show that higher ATOX1 levels in the tumor cell cytoplasm correlate with a trend towards better event-free survival after TM treatment for triple-negative breast cancer patients and patients at stage III of disease. In conclusion, ATOX1 may be a potential predictive biomarker for TM treatment of breast cancer patients at high risk of recurrence and should be tested in a larger cohort of patients.
Highlights
A recent phase II clinical trial tested the therapeutic efficacy of adjuvant tetrathiomolybdate (TM) following chemotherapy in triple-negative breast cancer (TNBC) patients, who showed no evidence of disease (NED), but were at high risk of recurrence
Copper depletion with TM is a promising treatment for breast cancer patients
Treatment of breast cancer patients highATOX1 risk ofisrecurdemonstrated at a median follow-up of 10.3 years with
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. We recently reported that ATOX1 stimulates directional breast cancer cell migration, a key step in metastasis, and that high tumor expression of ATOX1 significantly correlates with poor survival of breast cancer patients [5,6]. A recent phase II clinical trial tested the therapeutic efficacy of adjuvant tetrathiomolybdate (TM) following chemotherapy in triple-negative breast cancer (TNBC) patients, who showed no evidence of disease (NED), but were at high risk of recurrence. Given that the reliance on copper trafficking in metastasis might vary across the different molecular subtypes of breast cancer and subsequently influence the impact of copper depletion as a therapeutic strategy, we sought to evaluate ATOX1 as a predictive factor for TM treatment outcome of breast cancer patients at high risk of recurrence using tumor tissue sections and follow-up data from the phase II clinical trial described above
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