Open Access Highly Accessed Research article

Selecting for BRCA1 testing using a combination of homogeneous selection criteria and immunohistochemical characteristics of breast cancers

GianMaria Miolo12*, Vincenzo Canzonieri3, Clelia De Giacomi2, Lara Della Puppa1, Riccardo Dolcetti4, Davide Lombardi2, Tiziana Perin3, Simona Scalone2, Andrea Veronesi2 and Alessandra Viel1

Author Affiliations

1 Department of Molecular Oncology and Translational Research, Division of Experimental Oncology 1, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy

2 Department of Senology, Division of Medical Oncology C, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy

3 Department of Diagnostic Laboratories and Cell Therapy, Division of Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy

4 Department of Medical Oncology, Cancer Biommunotherapy Unit, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy

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BMC Cancer 2009, 9:360  doi:10.1186/1471-2407-9-360

Published: 10 October 2009

Abstract

Background

BRCA1 gene-related tumours are more frequently estrogen receptor (ER) and progesterone receptor (PR) negative with a lower prevalence of human epidermal growth factor receptor 2 (HER2) overexpression or amplification. We evaluated the effectiveness of a combination of homogeneously selected criteria and immunohistochemical (IHC) characteristics of Familial Breast Cancers (FBCs) in detecting BRCA1 mutation carriers.

Methods

Primary breast tumours from 93 FBC patients defined by specific eligibility criteria, based on personal and familial tumour history, were evaluated by Allred's method. The BRCA1 molecular analysis, including Multiplex Ligation-dependent Probe Amplification (MLPA), was considered as the gold standard assay.

Results

A total of 10 BRCA1 pathogenetic mutations was found. With the exclusion of the tumours characterized by double positive receptorial status and/or strong HER2 positivity (3+), we identified 22 patients, 10 of whom resulted as BRCA1 mutation carriers. The sensitivity, specificity, positive and negative predictive values were 100%, 83.3%, 45.4% and 100% respectively.

Conclusion

Our findings suggest that the IHC analysis by Allred's method improves our ability to select patients for BRCA1 testing.