title: 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.
abstract: 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.
authors.affiliation: Sarah Cannon Research Institute, 3322 West End Ave. Suite 900, Nashville, TN, 37203, USA. jhainsworth@tnonc.com.|Tennessee Oncology, PLLC, Nashville, TN, USA. jhainsworth@tnonc.com.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Tennessee Oncology, PLLC, Nashville, TN, USA.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Murphy
authors.affiliation: Florida Cancer Specialists, Clearwater, FL, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Alemar
authors.affiliation: Tennessee Oncology, PLLC, Chattanooga, TN, USA.
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Daniel
authors.affiliation: The Center for Cancer and Blood Disorders, Fort Worth, TX, USA.
authors.forename: Robyn R
authors.initials: RR
authors.lastname: Young
authors.affiliation: Sarah Cannon Research Institute, 3322 West End Ave. Suite 900, Nashville, TN, 37203, USA.|Tennessee Oncology, PLLC, Nashville, TN, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008875:Middle Aged; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019233:Retreatment; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: HER2 abnormalities; HER2-negative; PRO Onc assay