Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer

Abstract

Backgrounds The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known. Methods We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3–4 weeks later (first follow-up) were determined. Results The median follow-up time of the 52 enrolled patients was 655.0 days (18–1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival. Conclusions We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.

Analysis of Circulating Tumor Cells in Breast Cancer

“…Another study assessed the prognostic value of HER2 + CTCs in patients with metastatic breast cancer starting a new line of treatment. 44 At first follow-up, patients with HER2 + CTCs (who may have had HER2 + or HER2 – primary tumors) had significantly shorter progression-free and overall survivals than those without HER2 + CTCs.…”

HER2 amplification detected in the circulating DNA of patients with gastric cancer: a retrospective pilot study

“…Because solid tumours are known to comprise various subclones, which can show different genomic evolution over time and different responses to treatment [26], HER2 status in GC can change during progression and/or disease recurrence. In BC, the presence of HER2-positive tumour cells in recurrent cancer patients with HER2-negative primary tumours has been reported [27]. To overcome these difficulties, in this retrospective pilot study, we investigated the possible utility of plasma cfDNA as an additional source for detecting HER2 amplification and as additive information for predicting the therapeutic effect of trastuzumab treatment in patients with GC.…”

Site-specific DNA-antibody conjugates for specific and sensitive immuno-PCR

“…This finding is especially important because the relationship between the Her2 status of CTCs and the primary tumor is not clear. In this regard, it is known that Her2 þ tumors can convert to Her2 − status during progression, and patients with Her2 − primary tumors can have Her2 þ CTCs (36)(37)(38)(39). In the latter case, such patients could be candidates for Her2 specific therapy.…”