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.