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. 2020 Jun;181(3):679-689.
doi: 10.1007/s10549-020-05662-x. Epub 2020 May 4.

Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors

Chun Wang  1 , Zhaomei Mu  2 , Zhong Ye  1 , Zhenchao Zhang  1 , Maysa M Abu-Khalaf  1 , Daniel P Silver  1 , Juan P Palazzo  3 , Geetha Jagannathan  3 , Frederick M Fellin  1 , Saveri Bhattacharya  1 , Rebecca J Jaslow  1 , Theodore N Tsangaris  1 , Adam Berger  4 , Manish Neupane  1 , Terrence P Cescon  5 , AnaMaria Lopez  1 , Kaelan Yao  1 , Weelic Chong  1 , Brian Lu  1 , Ronald E Myers  1 , Lifang Hou  6 , Qiang Wei  7 , Bingshan Li  7 , Massimo Cristofanilli  8 , Hushan Yang  9
Affiliations

Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors

Chun Wang et al. Breast Cancer Res Treat. 2020 Jun.

Abstract

Purpose: Discordance between HER2 expression in tumor tissue (tHER2) and HER2 status on circulating tumor cells (cHER2) has been reported. It remains largely underexplored whether patients with tHER2-/cHER2+ can benefit from anti-HER2 targeted therapies.

Methods: cHER2 status was determined in 105 advanced-stage patients with tHER2- breast tumors. Association between cHER2 status and progression-free survival (PFS) was analyzed by univariate and multivariate Cox models and survival differences were compared by Kaplan-Meier method.

Results: Compared to the patients with low-risk cHER2 (cHER2+ < 2), those with high-risk cHER2 (cHER2+ ≥ 2) had shorter survival time and an increased risk for disease progression (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.20-3.88, P = 0.010). Among the patients with high-risk cHER2, those who received anti-HER2 targeted therapies had improved PFS compared with those who did not (HR 0.30, 95% CI 0.10-0.92, P = 0.035). In comparison, anti-HER2 targeted therapy did not affect PFS among those with low-risk cHER2 (HR 0.70, 95% CI 0.36-1.38, P = 0.306). Similar results were obtained after adjusting covariates. A longitudinal analysis of 67 patients with cHER2 detected during follow-ups found that those whose cHER2 status changed from high-risk at baseline to low-risk at first follow-up exhibited a significantly improved survival compared to those whose cHER2 remained high-risk (median PFS: 11.7 weeks vs. 2.0 weeks, log-rank P = 0.001).

Conclusion: In advanced-stage breast cancer patients with tHER2- tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.

Keywords: Breast cancer; Circulating tumor cell (CTC); Human epidermal growth factor receptor 2 (HER2); Progression-free survival (PFS).

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Conflict of interest statement

Conflicts of Interest: The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. HER2 expression in tumor tissue and circulating tumor cell.
(A) HER2-positive and HER2-negative breast tumors; (B) HER2-positive and HER2-negative CTCs. HER2, human epidermal growth factor receptor 2; CTC, circulating tumor cell.
Figure 2
Figure 2. Kaplan-Meier plots for patient outcomes.
Differences in progression-free survival were compared in risk groups stratified by (A) cHER2 status, or (B) cHER2 status in combination with anti-HER2 targeted therapies. cHER2, human epidermal growth factor receptor 2 phenotype on circulating tumor cell.
Figure 3
Figure 3. Dynamic changes in cHER2 status and patient outcomes.
(A) Associations between changes of cHER2 status from baseline to first follow-up and patient progression-free survival. Longitudinal monitoring of cHER2 status using serial blood samples collected from metastatic breast cancer patients with hormonal receptor (HR) positive (B) or HR-negative (C) tumor. cHER2, human epidermal growth factor receptor 2 phenotype on circulating tumor cell; PR, partial response; PD, progressive disease.
See this image and copyright information in PMC

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