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

Chun Wang, Zhaomei Mu, Zhong Ye, Zhenchao Zhang, Maysa M. Abu-Khalaf, Daniel P. Silver, Juan P. Palazzo, Geetha Jagannathan, Frederick M. Fellin, Saveri Bhattacharya, Rebecca J. Jaslow, Theodore N. Tsangaris, Adam Berger, Manish Neupane, Terrence P. Cescon, Ana Maria Lopez, Kaelan Yao, Weelic Chong, Brian Lu, Ronald E. MyersLifang Hou, Qiang Wei, Bingshan Li, Massimo Cristofanilli, Hushan Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)679-689
Number of pages11
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - Jun 1 2020


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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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