Concordance of the IHC4 Score Performed in Local or Central Laboratory to Endopredict in ER+/HER2- Breast Cancer

NCT ID: NCT04246606

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 155 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-04-24
• Study Completion Date: 2023-11-01

Brief Summary

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).

Detailed Description

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.

Conditions

Breast Neoplasm Female

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

ER+/HER2- infiltrating early breast cancer

Patients with ER+/HER2- infiltrating early breast cancer for which EndoPredict molecular signature was performed.

IHC4 score

Intervention Type: DIAGNOSTIC_TEST

The IHC4 score is a prognostic tool that incorporates immunohistochemical parameters of ER (H-score), PR (% of positive cells), HER2 (positive or negative status), and Ki67 (% of positive cells).

IHC4 score, combined with nodal status and tumor grade, age, and the type of endocrine therapy (tamoxifen or aromatase inhibitors) provides a clinical score IHC4+C.

IHC4+C provides a prognostic risk of distant recurrence at 10 years for patients who underwent endocrine therapy for 5 years. IHC4+C defined three distinct risk categories:

• <10%: low risk
• [10-20%]: intermediate risk
• >20%: high risk

Interventions

IHC4 score

The IHC4 score is a prognostic tool that incorporates immunohistochemical parameters of ER (H-score), PR (% of positive cells), HER2 (positive or negative status), and Ki67 (% of positive cells).

IHC4 score, combined with nodal status and tumor grade, age, and the type of endocrine therapy (tamoxifen or aromatase inhibitors) provides a clinical score IHC4+C.

IHC4+C provides a prognostic risk of distant recurrence at 10 years for patients who underwent endocrine therapy for 5 years. IHC4+C defined three distinct risk categories:

• <10%: low risk
• [10-20%]: intermediate risk
• >20%: high risk

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Roche Diagnostics GmbH

INDUSTRY

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juliette Haudebourg, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Antoine Lacassagne

Locations

Centre Antoine Lacassagne

Nice, , France

Countries

France

Other Identifiers

TRA05-GEFPICS

Identifier Type: -

Identifier Source: org_study_id