1. ¹Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
2. ²Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
3. ³Breast and Gynecological Group, Molecular Pathology Program, Spanish National Cancer Center (CNIO), Madrid, Spain
4. ⁴Department of Medicine, Division of Medical Genetics, University of Pennsylvania, Philadelphia, PA, USA
5. ⁵Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain

Correspondence: Dr J Benítez, Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Center for Biomedical Research on Rare Diseases (CIBERER), Melchor Fernández Almagro 3, Madrid 28029, Spain. E-mail: jbenitez@cnio.es

Received 11 September 2007; Revised 1 November 2007; Accepted 8 November 2007; Published online 10 December 2007.

Abstract

Five breast cancer subtypes have been described in sporadic breast cancer (SBC) using expression arrays: basal-like, ERBB2, normal breast-like, luminal A and B. These molecular subtypes show different genomic aberration patterns (GAPs). Recently, our group described these breast cancer subtypes in 50 non-BRCA1/2 familial tumors using immunohistochemistry assays. We extended this study to the other classes of familial breast cancer (FBC), including 62 tumors (18 BRCA1, 16 BRCA2 and 28 non-BRCA1/2), with the same panel of 25 immunohistochemical (IHC) markers and histological grade obtaining a similar classification. We combined these data with results generated by a 1 Mb BAC array-based CGH study to evaluate the genomic aberrations of each group. We found that BRCA1-related tumors are preferentially basal-like, whereas non-BRCA1/2 familial tumors are mainly luminal A subtype. We described distinct GAPs related to each IHC subtype. Basal tumors had a greater number of gains/losses, while luminal B tumors had more high-level DNA amplifications. Our data are similar to those obtained in SBC studies, highlighting the existence of distinct genetic pathways of tumor evolution, common to both SBC and FBC.