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Breast Cancer Res Treat (2016) 160:4149 DOI 10.1007/s10549-016-3969-7
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Web End = CLINICAL TRIAL
Use of a multiplexed immunoassay (PRO Onc assay) to detect HER2 abnormalities in circulating tumor cells of womenwith HER2-negative metastatic breast cancer: lack of response to HER2-targeted therapy
John D. Hainsworth1,2 Patrick B. Murphy2 Jose R. Alemar3 Brooke R. Daniel4
Robyn R. Young5 Denise A. Yardley1,2
Received: 15 June 2016 / Accepted: 29 August 2016 / Published online: 8 September 2016 Springer Science+Business Media New York 2016
AbstractPurpose 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 conrm the presence of a cohort that tested HER2-positive. After this nding was conrmed, 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.
Keywords HER2-negative HER2 abnormalities PRO
Onc assay
Introduction
The development of effective HER2-targeted therapy has markedly improved survival in the 2025 % of breast cancer patients with HER2-positive tumors [14]. At present, FISH analysis is considered the gold standard for identication of HER2-positive...