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Use of a multiplexed immunoassay (PRO Onc assay) to detect HER2 abnormalities in circulating tumor cells of women with HER2-negative metastatic breast cancer: lack of response to HER2-targeted therapy

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Abstract

Purpose

Determination of HER2 status by testing circulating tumor cells (CTCs), compared to sampling tumor biopsies, may improve patient management by allowing ongoing assessment of HER2 status during the disease course. The PRO Onc assay (Prometheus Laboratories; San Diego, CA) is a multiplexed immunoassay that measures the expression and activation of HER2 in CTCs. In this study, we screened patients with metastatic HER2-negative breast cancer with the PRO Onc assay; patients with HER2 overexpression or activation received a trial of HER2-targeted therapy.

Methods

In Part 1 of the trial, patients with HER2-negative breast cancer were screened with the PRO Onc assay to confirm the presence of a cohort that tested HER2-positive. After this finding was confirmed, patients in Part 2 of the study with HER2 abnormalities received a trial of treatment with trastuzumab/pertuzumab.

Results

In Part 1, 31 of 57 specimens contained CTCs; of these, 12 (38 %) showed HER2 abnormalities by PRO Onc assay. In Part 2, 129 of 226 patients (57 %) had CTCs; 24 of these patients (19 %) had HER2 abnormalities detected. Fourteen patients were treated with HER2-targeted therapy. Twelve of 14 patients progressed within 6 weeks, one patient had a brief (12 weeks) partial response, and one patient was stable for 12 weeks.

Conclusions

HER2 overexpression or activation was detected by the PRO Onc assay in 22 % of HER2-negative patients with CTCs. However, HER2-targeted therapy was not effective in such patients. FISH and IHC staining remain the standards for HER2 determination.

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Acknowledgments

This study was supported in part by Grants from Prometheus Labs and Genentech-Roche.

Author information

Authors and Affiliations

  1. Sarah Cannon Research Institute, 3322 West End Ave. Suite 900, Nashville, TN, 37203, USA

    John D. Hainsworth & Denise A. Yardley

  2. Tennessee Oncology, PLLC, Nashville, TN, USA

    John D. Hainsworth, Patrick B. Murphy & Denise A. Yardley

  3. Florida Cancer Specialists, Clearwater, FL, USA

    Jose R. Alemar

  4. Tennessee Oncology, PLLC, Chattanooga, TN, USA

    Brooke R. Daniel

  5. The Center for Cancer and Blood Disorders, Fort Worth, TX, USA

    Robyn R. Young

Authors
  1. John D. Hainsworth
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  2. Patrick B. Murphy
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  3. Jose R. Alemar
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  4. Brooke R. Daniel
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  5. Robyn R. Young
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  6. Denise A. Yardley
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Corresponding author

Correspondence to John D. Hainsworth.

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Conflict of interest

JDH received funding to his institution for the study from Genentech and Prometheus. All the other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

https://clinicaltrials.gov/ct2/show/record/NCT01048099

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Hainsworth, J.D., Murphy, P.B., Alemar, J.R. et al. Use of a multiplexed immunoassay (PRO Onc assay) to detect HER2 abnormalities in circulating tumor cells of women with HER2-negative metastatic breast cancer: lack of response to HER2-targeted therapy. Breast Cancer Res Treat 160, 41–49 (2016). https://doi.org/10.1007/s10549-016-3969-7

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  • DOI: https://doi.org/10.1007/s10549-016-3969-7

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