Changes of HER2 status has been reported in circulating tumor cells (CTC) isolated from preclinical models and metastatic breast cancer (MBC) patients. The prospective multicentric phase II “CirCe T-DM1” trial was set up to assess whether HER2-amplified CTC are detectable in HER2-negative MBC and whether these cancers would respond to anti-HER2 therapy.
HER2-amplified CTC were screened in HER2-negative (HER2-/ER- and HER2-/ER+) MBC patients starting a 3rd line or 4th line of systemic therapy. CTC were detected by CellSearch® (Janssen Diagnostics) and FISH was performed on isolated CTCs. HER2-amplification was defined by a HER2/CEP17 ratio ≥2.2. Patients with ≥1 HER2-amplified CTC, measurable disease and adequate organ function were eligible. After stratification according to amplified CTC count (< vs ≥ 3), patients received single agent T-DM1. The primary endpoint of the study was the response rate by RECIST criteria.
From 11/2013 to 08/2016, 155 MBC patients were screened. 11 (9.2%) and 3 patients (2.5%) had 1-2 and ≥3 HER2-amplified CTCs respectively (minimal HER2/CEP17 ratio: 2.5). In the 14 patients with HER2-amplified CTC, the fraction of HER2-amplified CTCs among all detected CTCs was low (median 1.6%, range [0.3%-35.3%]), and presence of HER2-amplified CTCs was not associated with any patients’ characteristics. 11 patients were treated with single agent T-DM1. Partial response was confirmed in one patient with 1 HER2-amplified CTC (among 9 CTC detected); median PFS was 4.9 months (range: 1.8-10.1).
This study shows that CTCs with a true HER2-amplification can be detected in advanced HER2-negative MBC, mostly as a minor CTCs subset. Although one confirmed response was observed in our study, the overall low response rate to specific anti-HER2 therapy does not support the clinical utility of such strategy in that setting.
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All authors have declared no conflicts of interest.