Articles were selected for inclusion in the systematic review of the evidence if they met the following criteria: (1) the study compared, prospectively or retrospectively, fluorescent ISH (FISH) and immunohistochemistry (IHC) results or other tests; described technical comparisons across various assay platforms; examined potential testing algorithms for HER2 testing; or examined the correlation of HER2 status in primary versus metastatic tumors from the same patients; (2) the study population consisted of patients with a diagnosis of invasive breast cancer; or (3) the primary outcomes included the negative predictive value (NPV) or positive predictive value (PPV) of ISH and IHC assays used to determine HER2 status, alone and in combination; negative and positive concordance across platforms; and accuracy in determining HER2 status and benefit from anti-HER2 therapy and in determining sensitivity and specificity of individual tests. Consideration was given to studies that directly compared results across assay platforms.
Studies were not limited to randomized controlled trials but also included other study types, including cohort designs, case series, evaluation studies, and comparative studies. The Update Committee also reviewed other testing guidelines and proficiency strategies of various US and international organizations, including unpublished data. Letters, commentaries, and editorials were reviewed for any new information. Case reports were excluded. The clinical questions addressed in the update are available inData Supplement 5 .
This information was used to help the Update Committee develop new algorithms (for pathologists and oncologists) for testing, specify testing requirements and exclusions, and facilitate the necessary quality assurance monitoring that will make HER2 testing less variable and ensure more analytic consistency between laboratories. The term ratio, as used in the guideline recommendations and algorithms, always applies to the HER2/CEP17 ratio, which means the ratio of HER2 signals per cell (numerator) over CEP17 signals per cell (denominator).
Studies were not limited to randomized controlled trials but also included other study types, including cohort designs, case series, evaluation studies, and comparative studies. The Update Committee also reviewed other testing guidelines and proficiency strategies of various US and international organizations, including unpublished data. Letters, commentaries, and editorials were reviewed for any new information. Case reports were excluded. The clinical questions addressed in the update are available in
This information was used to help the Update Committee develop new algorithms (for pathologists and oncologists) for testing, specify testing requirements and exclusions, and facilitate the necessary quality assurance monitoring that will make HER2 testing less variable and ensure more analytic consistency between laboratories. The term ratio, as used in the guideline recommendations and algorithms, always applies to the HER2/CEP17 ratio, which means the ratio of HER2 signals per cell (numerator) over CEP17 signals per cell (denominator).
