title: The Genomic Landscape of Male Breast Cancers.
abstract: OBJECTIVE
  Male breast cancer is rare, and its genomic landscape has yet to be fully characterized. Lacking studies in men, treatment of males with breast cancer is extrapolated from results in females with breast cancer. We sought to define whether male breast cancers harbor somatic genetic alterations in genes frequently altered in female breast cancers.
  
  
  METHODS
  All male breast cancers were estrogen receptor-positive, and all but two were HER2-negative. Fifty-nine male breast cancers were subtyped by immunohistochemistry, and tumor-normal pairs were microdissected and subjected to massively parallel sequencing targeting all exons of 241 genes frequently mutated in female breast cancers or DNA-repair related. The repertoires of somatic mutations and copy number alterations of male breast cancers were compared with that of subtype-matched female breast cancers.
  
  
  RESULTS
  Twenty-nine percent and 71% of male breast cancers were immunohistochemically classified as luminal A-like or luminal B-like, respectively. Male breast cancers displayed a heterogeneous repertoire of somatic genetic alterations that to some extent recapitulated that of estrogen receptor (ER)-positive/HER2-negative female breast cancers, including recurrent mutations affecting PIK3CA (20%) and GATA3 (15%). ER-positive/HER2-negative male breast cancers, however, less frequently harbored 16q losses, and PIK3CA and TP53 mutations than ER-positive/HER2-negative female breast cancers. In addition, male breast cancers were found to be significantly enriched for mutations affecting DNA repair-related genes.
  
  
  CONCLUSIONS
  Male breast cancers less frequently harbor somatic genetic alterations typical of ER-positive/HER2-negative female breast cancers, such as PIK3CA and TP53 mutations and losses of 16q, suggesting that at least a subset of male breast cancers are driven by a distinct repertoire of somatic changes. Given the genomic differences, caution may be needed in the application of biologic and therapeutic findings from studies of female breast cancers to male breast cancers. Clin Cancer Res; 22(16); 4045-56. ©2016 AACR.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Piscuoglio
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Charlotte K Y
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Murray
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Pathology, European Institute of Oncology, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Guerini-Rocco
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Luciano G
authors.initials: LG
authors.lastname: Martelotto
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Pathology, Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa, São Paulo, Brazil.
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Geyer
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Francois-Clement
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Samuel
authors.initials: S
authors.lastname: Berman
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fusco
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Sakr
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Carey A
authors.initials: CA
authors.lastname: Eberle
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Leticia
authors.initials: L
authors.lastname: De Mattos-Arruda
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Macedo
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Akram
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. Department of Molecular and Cellular Biology, Stony Brook University, Stony Brook, New York. Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Timour
authors.initials: T
authors.lastname: Baslan
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
authors.forename: James B
authors.initials: JB
authors.lastname: Hicks
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Tari A
authors.initials: TA
authors.lastname: King
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Edi
authors.initials: E
authors.lastname: Brogi
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. reisfilj@mskcc.org.
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D018567:Breast Neoplasms, Male / Q000175:diagnosis / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017698:Postmenopause; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor