Real-time HER2 status detected on circulating tumor cells predicts different outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer patients

Shaohua Zhang, Lei Li, Tao Wang, Li Bian, Haixu Hu, Chunhong Xu, Bing Liu, Yi Liu, Massimo Cristofanilli, Zefei Jiang, Shaohua Zhang, Lei Li, Tao Wang, Li Bian, Haixu Hu, Chunhong Xu, Bing Liu, Yi Liu, Massimo Cristofanilli, Zefei Jiang

Abstract

Background: This study was initiated to investigate the difference in HER2 status between tumor tissue and circulating tumor cells (CTCs), as well as the predictive value of CTC HER2 status for predicting the outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer (MBC) patients.

Methods: HER2 expression on CTCs was detected using a CellSearch system within 7 days before a new line of anti-HER2 therapy was begun. According to the criterion proposed in our previous report, patients were defined as CTC HER2-positive or -negative. After close follow-up, the correlation between CTC HER2 status and the outcome of the treatment was evaluated by statistical analysis.

Results: CTCs were detected in 57.4 % (58/101) of the patients. Notably, 62.1 % (36/58) of these patients had an inconsistent HER2 status between their tissue and CTCs. The discordant rate may correlate with the time interval between histological and CTC HER2 testing and is more likely to occur in the subgroup of patients with an interval of > 1 year than in those with an interval < 1 year (70.7 % vs. 41.2 %, P = 0.043). For PFS, positive HER2 status on CTCs was shown to be a valuable predictor, both in univariate (HR = 0.321, 95%CI, 0.156-0.62, P = 0.0011) and multivariate (HR = 0.383, 95%CI, 0.166-0.831, P = 0.019) Cox regression analysis. Meanwhile, Kaplan-Meier survival curves revealed that the median PFS of CTC HER2-positive patients was significantly longer than CTC HER2-negative ones (8.5 vs. 3.5 months, P < 0.001).

Conclusions: HER2 status on CTCs was different from that of tumor tissues and predicted a different outcome of the patients' anti-HER2 therapy. This difference may be correlated with the time interval between tissue and CTC HER2 testing, indicating the necessity of real-time HER2 analysis for histologically HER2-positive MBC patients.

Keywords: Anti-HER2 therapy; Circulating Tumor Cells (CTCs); Human Epidermal Growth Factor Receptor 2 (HER2); Metastatic Breast Cancer (MBC); Real-time HER2 status.

Figures

Fig. 1
Fig. 1
Representative images for the 0, 1+, 2+, and 3+ intensities of HER2 expression on CTCs
Fig. 2
Fig. 2
Kaplan-Meier PFS plots of CTC HER2-positive and-negative patients. PFS was calculated from the time of the baseline blood draw. The coordinates of the dashed lines indicate the median survival time
Fig. 3
Fig. 3
Kaplan-Meier PFS plots of CTC HER2-positive and -negative patients in subgroups of time interval (between tissue and CTC HER2 testing) > 1 year (a) and < 1 year (b). PFS was calculated from the time of the baseline blood draw. The coordinates of the dashed lines indicate median survival time

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Source: PubMed

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