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The Genomic Landscape of Male Breast Cancers.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Aug 15; Vol. 22 (16), pp. 4045-56. Date of Electronic Publication: 2016 Mar 09. - Publication Year :
- 2016
-
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.<br />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.<br />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.<br />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.<br /> (©2016 American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Breast Neoplasms genetics
Breast Neoplasms metabolism
Breast Neoplasms, Male diagnosis
Comparative Genomic Hybridization
DNA Copy Number Variations
Female
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Male
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Staging
Postmenopause
Tumor Burden
Biomarkers, Tumor
Breast Neoplasms, Male genetics
Genetic Predisposition to Disease
Genomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 22
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 26960396
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-15-2840