The genomic landscape of male breast cancers Journal Article

Authors: Piscuoglio, S.; Ng, C. K. Y.; Murray, M. P.; Guerini-Rocco, E.; Martelotto, L. G.; Geyer, F. C.; Bidard, F. C.; Berman, S.; Fusco, N.; Sakr, R. A.; Eberle, C. A.; De Mattos-Arruda, L.; Macedo, G. S.; Akram, M.; Baslan, T.; Hicks, J. B.; King, T. A.; Brogi, E.; Norton, L.; Weigelt, B.; Hudis, C. A.; Reis-Filho, J. S.
Article Title: The genomic landscape of male breast cancers
Abstract: Purpose: 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. Experimental Design: 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. © 2016 AACR. © 2016 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 22
Issue: 16
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2016-08-01
Start Page: 4045
End Page: 4056
Language: English
DOI: 10.1158/1078-0432.ccr-15-2840
PROVIDER: scopus
PMCID: PMC4987160
PUBMED: 26960396
Notes: Article -- Export Date: 1 September 2016 -- Source: Scopus
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MSK Authors
  1. Clifford Hudis
    839 Hudis
  2. Larry Norton
    558 Norton
  3. Melissa P Murray
    93 Murray
  4. Tari King
    165 King
  5. Rita Sakr
    59 Sakr
  6. Edi Brogi
    304 Brogi
  7. Muzaffar M Akram
    90 Akram
  8. Carey Eberle
    17 Eberle
  9. Samuel Hart Berman
    17 Berman
  10. Britta Weigelt
    260 Weigelt
  11. Jorge Sergio Reis
    283 Reis
  12. Francois-Clement Bidard
    17 Bidard
  13. Kiu Yan Charlotte Ng
    152 Ng
  14. Nicola Fusco
    28 Fusco
  15. Timour Baslan
    15 Baslan