Concordance of the IHC4 Score Performed in Local or Central Laboratory to Endopredict in ER+/HER2- Breast Cancer
Concordance of the IHC4 Score Performed in Local or Central Laboratory to Endopredict in ER+/HER2- Breast Cancer
Retrospective observational, multicentric study assessing the immunohistochemistry (IHC)
 based test IHC4 score in infiltrating early breast cancer: comparison of the score performed
 in local laboratory vs in a central laboratory and concordance with a molecular gold standard
 classifier (EndoPredict).
The IHC4 prognostic signature is an algorithm based on a combination of biomarkers evaluated
 in immunohistochemistry and anatomical-clinical parameters. Immunohistochemistry is routinely
 performed as a diagnostic procedure for estrogen receptor (ER; H-score 0-300), progesterone
 receptor (PR; % of marked cells), HER2 (positive vs negative status) and Ki67 (% of marked
 cells evaluated by counting). Clinical parameters include lymph node status (0N+, 1-3N+,
 >3N+, >3N+), tumour size in mm (≤10mm, 11-20, 21-50, >50mm), histologic grade (1, 2, 3),
 patient's age at diagnosis (<65 years, ≥65 years), and type of treatment (anti-estrogen or
 aromatase inhibitors).

 The method for reading and scoring conditions is very precise and currently guarantee the
 validity of the test (validated centrally in TransATAC). However, there is not yet an open
 access web platform available for the calculation of the IHC4 score, due to the prior need
 for homogenisation of the interpretation of immunochemistry (standardisation of the protocol)
 to generate a reliable and validated IHC4 under decentralised "real life" conditions. There
 is currently few published data on the weight of technical parameters (antibody clones,
 automaton type, etc.) or interpretation methods (scoring) in the calculation of the IHC4
 score (IHC4 robustness). However, only one study, published recently, shows a good tolerance
 of the test to variations in technical protocol or reading.

 In this context, a study coordinated by the GEFPICS group, composed of expert pathologists in
 breast cancer, has been set up to better define the robustness and the scope of IHC4 score.
 These project will assess 2 main aspects: (i) validate the local "real life" technique for
 the calculation of the IHC4 score; and (ii) homogenise the IHC reading method (especially for
 Ki67), on a cohort of cases from the GEFPICS, tested in a prognostic molecular signatures.
Sample selection criteria:

 1. Prior information of the patient.

 2. Histologically proven invasive breast cancer,

 3. ER-positive breast cancer, according to the following criteria: ER ≥10 % (local
 assessment)

 4. HER2-negative tumor by IHC (score 0 or 1+) and/or fluorescent in situ hybridization
 (FISH)/chromogenic in situ hybridization (CISH) negative (local assessment)

 5. IHC staining slides for ER, PR, KI67 and HER2 carry out on surgical resection
 according to local protocol available,

 6. In situ hybridization (ISH) staining for HER2 carry out on surgical resection, in case
 of IHC 2+ for HER2 immunostaining

 7. EndoPredict test results available (EPclin),

 8. Formalin-fixed and paraffin-embedded (FFPE) block from surgical resection of the
 primary tumor available,

 9. Patient ≥18 years old.