title: Biomarker testing for breast, lung, and gastroesophageal cancers at NCI designated cancer centers.
abstract: BACKGROUND
  Molecular biomarkers, a cornerstone of precision oncology, are critical in breast, gastroesophageal, and non-small cell lung cancer management (BC, GEC, NSCLC). Testing practices are intensely debated, impacting diagnostic quality and affecting pathologists, oncologists and patients. However, little is known about testing approaches used in practice. Our study described biomarker practices in BC, GEC, and NSCLC at the leading US cancer centers.
  
  
  METHODS
  We conducted a survey of the National Cancer Institute (NCI) designated centers on BC, GEC, and NSCLC biomarker testing. We used simple frequencies to describe practices, two-sided Fisher's exact test and two-sided McNemar's test for cross-cancer comparison. All statistical tests were two-sided.
  
  
  RESULTS
  For BC human epidermal growth factor receptor 2 (HER2), 39% of centers combine guidelines by using in situ hybridization (ISH) and immunohistochemistry (IHC) concurrently, and 21% reflex-test beyond guideline-recommended IHC2+. For GEC HER2, 44% use ISH and IHC concurrently, and 28% reflex-test beyond IHC2+. In NSCLC, the use of IHC is limited to 4% for epidermal growth factor receptor (EGFR) and 7% for anaplastic lymphoma kinase (ALK). 43.5% test NSCLC biomarkers on oncologist order; 34.5% run all biomarkers upfront, and 22% use a sequential protocol. NSCLC external testing is statistically significantly higher than BC (P < .0001) and GEC (P < .0001). NSCLC internally developed tests are statistically significantly more common than BC (P < .0001) and GEC (P < .0001).
  
  
  CONCLUSIONS
  At the NCI cancer centers, biomarker testing practices vary, but exceeding guidelines is a common practice for established biomarkers and emerging practice for newer biomarkers. Use of internally developed tests declines as biomarkers mature. Implementation of multibiomarker protocols is lagging. Our study represents a step toward developing a biomarker testing practice landscape.
authors.affiliation: * Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Schink
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Trosman
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Weldon
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Kalliopi P
authors.initials: KP
authors.lastname: Siziopikou
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Rademaker
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Jyoti D
authors.initials: JD
authors.lastname: Patel
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL (JCS, JRT, CBW, KPS, AWR, JDP, ABB, WJG); Center for Business Models in Healthcare, Chicago, IL (JRT, CBW); UCSF Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California, San Francisco, CA (JRT); Department of Pathology, Dartmouth Hitchcock Medical Center and the Audrey and Theodor Geisel School of Medicine, Dartmouth College, Lebanon, NH (GJT); Mayo Clinic Cancer Center, Mayo Clinic, Jacksonville, FL (EAP).* Current affiliation: Spectrum Health Medical Group, Grand Rapids, MI. w-gradishar@northwestern.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Gradishar
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry*; D002173:Cancer Care Facilities; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry; D015986:Confounding Factors, Epidemiologic; D003430:Cross-Sectional Studies; D066246:ErbB Receptors / Q000032:analysis; D004938:Esophageal Neoplasms / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020407:Internet; D008175:Lung Neoplasms / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D054547:National Cancer Institute (U.S.); D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data* / Q000639:trends; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D057566:Self Report; D013274:Stomach Neoplasms / Q000737:chemistry*; D011795:Surveys and Questionnaires; D014481:United States; D018631:ras Proteins / Q000032:analysis
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018631:ras Proteins; C117307:KRAS protein, human; C000626173:ALK protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human