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

  • Epidemiology
  • Published:
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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.

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Funding

This study was funded by National Cancer Institute Grant (R01CA207468), Pennsylvania Department of Health Grant (SAP# 4100062221), The Inflammatory Breast Cancer Network Foundation, The Jamie Lieberman Memorial Endowment Fund. Research reported in this publication utilized the Circulating Tumor Cell Core Facility at the Sidney Kimmel Cancer Center at Jefferson Health and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA056036. The funding agencies were not involved in the design, conduct, analysis or interpretation of the study.

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Authors and Affiliations

  1. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Chun Wang, Zhong Ye, Zhenchao Zhang, Maysa M. Abu-Khalaf, Daniel P. Silver, Frederick M. Fellin, Saveri Bhattacharya, Rebecca J. Jaslow, Theodore N. Tsangaris, Manish Neupane, AnaMaria Lopez, Kaelan Yao, Weelic Chong, Brian Lu, Ronald E. Myers & Hushan Yang

  2. Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

    Zhaomei Mu & Massimo Cristofanilli

  3. Department of Pathology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Juan P. Palazzo & Geetha Jagannathan

  4. Department of Surgery, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Adam Berger

  5. Department of Hematology Oncology, Reading Hospital, West Reading, PA, 19611, USA

    Terrence P. Cescon

  6. Department of Preventive Medicine, Northwestern University, Chicago, IL, 60611, USA

    Lifang Hou

  7. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37235, USA

    Qiang Wei & Bingshan Li

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  1. Chun Wang
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  2. Zhaomei Mu
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  3. Zhong Ye
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  4. Zhenchao Zhang
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  5. Maysa M. Abu-Khalaf
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  6. Daniel P. Silver
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  9. Frederick M. Fellin
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  20. Ronald E. Myers
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  21. Lifang Hou
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  22. Qiang Wei
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  24. Massimo Cristofanilli
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Correspondence to Massimo Cristofanilli or Hushan Yang.

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Wang, C., Mu, Z., Ye, Z. et al. Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors. Breast Cancer Res Treat 181, 679–689 (2020). https://doi.org/10.1007/s10549-020-05662-x

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