Internal Quality Assurance Program for ERBB2 (HER2) Testing Improves the Selection of Breast Cancer Patients for Treatment with Trastuzumab

International guidelines for ERBB2 (HER2) testing procedures in breast cancer patients highlight the importance of external quality control. In contrast, internal quality assurance programs have been poorly defined, and their clinical significance has not yet been investigated. We developed a quality assurance scheme by performing HER2 FISH on 724 patients randomly selected out of 1996 patients with breast cancer presenting at our institute. We collected samples monthly for tissue microarray analysis and correlated HER2 gene status with IHC scores. The concordance was excellent ( , ). HER2 amplification characterized 25% of score 2+ but also 13% of score 1+, thus expanding the number of patients eligible for trastuzumab. Based on these findings, the FISH test is now recommended at our institution for score 1+ and 2+ patients. Adherence to internal assurance program improves patient selection and may lead to the definition of in-house tailored diagnostic algorithms different from those proposed in international guidelines. 1. Introduction ERBB2 (commonly referred to as HER2) protein overexpression or gene amplification is a predictive marker for response to trastuzumab (Herceptin) in patients with breast cancer (BC) [1, 2]. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the only tests currently approved by the Federal Drug Administration (FDA) and by the European Medicines Agency (EMA) for HER2 testing. In clinical practice, patients may be considered eligible for treatment with trastuzumab if classified as score 3+ by IHC or if they carry gene amplification as detected by FISH. In contrast, patients showing score 0 or 1+ by IHC or the absence of gene amplification by FISH should not be submitted to targeted therapy. The American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) strongly recommend that patients with equivocal results by IHC (i.e., score 2+) should be further investigated by FISH to confirm eligibility [3]. The importance of external quality proficiency assessment for HER2 testing has been emphasized by the ASCO/CAP and by the United Kingdom National External Quality Assurance Scheme (UK-NEQAS) [4–6]. In contrast, although strongly recommended by the ASCO/CAP, internal quality assurance programs have been weakly defined and their clinical significance has been poorly investigated. Thus, the aim of this study was to develop a reliable and effective internal quality assurance scheme and to determine its influence on patients management. 2. Materials and Methods 2.1. Patients From