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Loss of 16q in high grade breast cancer is associated with estrogen receptor status: Evidence for progression in tumors with a luminal phenotype?
Author(s) -
Natrajan Rachael,
Lambros Maryou B. K.,
Geyer Felipe C.,
Marchio Caterina,
Tan David S. P.,
Vatcheva Radost,
Shiu KaiKeen,
Hungermann Daniela,
RodriguezPinilla Socorro Maria,
Palacios Jose,
Ashworth Alan,
Buerger Horst,
ReisFilho Jorge S.
Publication year - 2009
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20646
Subject(s) - breast cancer , estrogen receptor , phenotype , cancer , progesterone receptor , cancer research , tumor progression , biology , estrogen , medicine , pathology , oncology , gene , genetics
Loss of the long arm of chromosome 16 (16q) is observed in the vast majority of low grade/grade I (GI) invasive ductal carcinomas of no special type (IDC‐NSTs), whereas this event is uncommonly seen in high grade/grade III (GIII) IDC‐NSTs. Together with data on the pathology and genetics of breast cancer recurrences, this has led to the proposal that GI and GIII breast cancers evolve through distinct genetic pathways and that progression from GI to GIII is an unlikely biological phenomenon. We compared the genomic profiles of GIII‐IDC‐NSTs with 16q whole arm loss (16qWL) according to estrogen receptor (ER) status. 16qWL was found in 36.5% of cases and was significantly associated with ER expression and luminal phenotype. ER+ GIII‐IDC‐NSTs with 16qWL displayed significantly higher levels of genomic instability than ER+ IDC‐NSTs without 16qWL. Furthermore, ER+ and ER− IDC‐NSTs stratified according to the presence of 16qWL harbored distinct patterns of genetic aberrations. Interestingly, ER+/16qWL tumors displayed genetic features usually found in tumors with homologous DNA repair defects and significantly more frequently harbored heterozygous loss of BRCA2 than the remaining ER+ cancers. Our results demonstrate that approximately one third of GIII tumors harbor 16qWL, confirming that progression from low to high grade breast cancer is not found in the majority of breast cancers. 16qWL was significantly more prevalent in ER+/luminal GIII‐IDC‐NSTs. Given that GI breast cancers harbor a luminal phenotype, our results suggest that if progression from GI to GIII breast cancer does happen, it may preferentially occur in breast cancers of luminal phenotype. © 2009 Wiley‐Liss, Inc.