PMID- 22333393
OWN - NLM
STAT- MEDLINE
DCOM- 20130207
LR  - 20240512
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 14
IP  - 1
DP  - 2012 Feb 14
TI  - Gene expression profiling of primary male breast cancers reveals two unique 
      subgroups and identifies N-acetyltransferase-1 (NAT1) as a novel prognostic 
      biomarker.
PG  - R31
AB  - INTRODUCTION: Male breast cancer (MBC) is a rare and inadequately characterized 
      disease. The aim of the present study was to characterize MBC tumors 
      transcriptionally, to classify them into comprehensive subgroups, and to compare 
      them with female breast cancer (FBC). METHODS: A total of 66 
      clinicopathologically well-annotated fresh frozen MBC tumors were analyzed using 
      Illumina Human HT-12 bead arrays, and a tissue microarray with 220 MBC tumors was 
      constructed for validation using immunohistochemistry. Two external gene 
      expression datasets were used for comparison purposes: 37 MBCs and 359 FBCs. 
      RESULTS: Using an unsupervised approach, we classified the MBC tumors into two 
      subgroups, luminal M1 and luminal M2, respectively, with differences in tumor 
      biological features and outcome, and which differed from the intrinsic subgroups 
      described in FBC. The two subgroups were recapitulated in the external MBC 
      dataset. Luminal M2 tumors were characterized by high expression of immune 
      response genes and genes associated with estrogen receptor (ER) signaling. 
      Luminal M1 tumors, on the other hand, despite being ER positive by 
      immunohistochemistry showed a lower correlation to genes associated with ER 
      signaling and displayed a more aggressive phenotype and worse prognosis. 
      Validation of two of the most differentially expressed genes, class 1 human 
      leukocyte antigen (HLA) and the metabolizing gene N-acetyltransferase-1 (NAT1), 
      respectively, revealed significantly better survival associated with high 
      expression of both markers (HLA, hazard ratio (HR) 3.6, P = 0.002; NAT1, HR 2.5, 
      P = 0.033). Importantly, NAT1 remained significant in a multivariate analysis (HR 
      2.8, P = 0.040) and may thus be a novel prognostic marker in MBC. CONCLUSIONS: We 
      have detected two unique and stable subgroups of MBC with differences in tumor 
      biological features and outcome. They differ from the widely acknowledged 
      intrinsic subgroups of FBC. As such, they may constitute two novel subgroups of 
      breast cancer, occurring exclusively in men, and which may consequently require 
      novel treatment approaches. Finally, we identified NAT1 as a possible prognostic 
      biomarker for MBC, as suggested by NAT1 positivity corresponding to better 
      outcome.
FAU - Johansson, Ida
AU  - Johansson I
AD  - Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, SE 
      22185 Lund, Sweden.
FAU - Nilsson, Cecilia
AU  - Nilsson C
FAU - Berglund, Pontus
AU  - Berglund P
FAU - Lauss, Martin
AU  - Lauss M
FAU - Ringner, Markus
AU  - Ringner M
FAU - Olsson, Hakan
AU  - Olsson H
FAU - Luts, Lena
AU  - Luts L
FAU - Sim, Edith
AU  - Sim E
FAU - Thorstensson, Sten
AU  - Thorstensson S
FAU - Fjallskog, Marie-Louise
AU  - Fjallskog ML
FAU - Hedenfalk, Ingrid
AU  - Hedenfalk I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120214
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Isoenzymes)
RN  - EC 2.3.1.5 (Arylamine N-Acetyltransferase)
RN  - EC 2.3.1.5 (N-acetyltransferase 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Arylamine N-Acetyltransferase/genetics/*metabolism
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Breast Neoplasms, Male/classification/diagnosis/*enzymology/mortality
MH  - Carcinoma, Ductal, Breast/classification/diagnosis/*enzymology/mortality
MH  - Carcinoma, Intraductal, 
      Noninfiltrating/classification/diagnosis/*enzymology/mortality
MH  - Cluster Analysis
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Isoenzymes/genetics/*metabolism
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Oligonucleotide Array Sequence Analysis
MH  - Principal Component Analysis
MH  - Prognosis
MH  - Statistics, Nonparametric
MH  - Tissue Array Analysis
MH  - *Transcriptome
MH  - Young Adult
PMC - PMC3496149
EDAT- 2012/02/16 06:00
MHDA- 2013/02/08 06:00
PMCR- 2012/02/14
CRDT- 2012/02/16 06:00
PHST- 2011/08/04 00:00 [received]
PHST- 2012/01/09 00:00 [revised]
PHST- 2012/02/14 00:00 [accepted]
PHST- 2012/02/16 06:00 [entrez]
PHST- 2012/02/16 06:00 [pubmed]
PHST- 2013/02/08 06:00 [medline]
PHST- 2012/02/14 00:00 [pmc-release]
AID - bcr3116 [pii]
AID - 10.1186/bcr3116 [doi]
PST - epublish
SO  - Breast Cancer Res. 2012 Feb 14;14(1):R31. doi: 10.1186/bcr3116.