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
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.
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.
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.
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.
KeywordsHER2-negative HER2 abnormalities PRO Onc assay
This study was supported in part by Grants from Prometheus Labs and Genentech-Roche.
Compliance with ethical standards
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.
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 was obtained from all individual participants included in the study.
- 9.Fehm T, Muller V, Aktas B et al (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective multicenter trial. Breast Cancer Res Treat 102:1495–1502Google Scholar
- 11.Liu L, Kim P, Liu X et al (2009) Novel method to detect activation of ErbB family receptor tyrosine kinases. AACR, Denver (#5260) Google Scholar
- 14.Cobleigh MA, Vogel CA, Tripathy D et al (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17:2639–2648PubMedGoogle Scholar
- 24.Wakelee HA et al (2016) Epidermal growth factor receptor (EGFR) genotyping of matched urine, plasma and tumor tissue from non-small cell lung cancer (NSCLC) patients treated with rociletinib. J Clin Oncol 34(Suppl):456s (Abstract #9001) Google Scholar
- 25.Kurbacher CM et al (2016) Anti-HER2 treatment in advanced metastatic HER2-negative breast cancer patients with elevated serum levels of the HER2 extracellular domain and/or HER2 overexpressing circulating tumor cells. J Clin Oncol 34(Suppl):33s (Abstract #597) Google Scholar
- 26.Albrecht S, Schochter F, Melcher CA et al (2014) DETECT III/IV: two combined clinical trials based on the phenotype of circulating tumor cells (CTCs). J Clin Oncol 32(Suppl):727s (Abstract TPS11132) Google Scholar