Background: The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis.\nYet, CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the\nabundance of CTCs remain elusive.\nMethods: We conducted CTC isolation and enumeration in a selected group of 73 consecutive patients characterized\nby progressive invasive breast cancer, high tumor load and treatment discontinuation at the time of CTC isolation.\nCTCs were quantified with the Parsortix microfluidic device. Clinicopathological variables, blood counts at the\ntime of CTC isolation and detailed treatment history prior to blood sampling were evaluated for each patient.\nResults: Among 73 patients, we detected at least one CTC per 7.5 ml of blood in 34 (46%). Of these, 22 (65%)\nhad single CTCs only, whereas 12 (35%) featured both single CTCs and CTC clusters. Treatment with the monoclonal\nantibody denosumab correlated with the absence of CTCs, both when considering all patients and when considering\nonly those with bone metastasis. We also found that low red blood cell count was associated with the presence of\nCTCs, whereas high CA 15-3 tumor marker, high mean corpuscular volume, high white blood cell count and high\nmean platelet volume associated specifically with CTC clusters.\nConclusions: In addition to blood count correlatives to single and clustered CTCs, we found that denosumab\ntreatment associates with most patients lacking CTCs from their peripheral circulation. Prospective studies will\nbe needed to validate the involvement of denosumab in the prevention of CTC generation.
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