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Medline ® Abstract for Reference 80

of 'Epidemiology, risk factors and the clinical approach to ER/PR negative, HER2-negative (Triple-negative) breast cancer'

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Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer.
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Iglesia MD, Vincent BG, Parker JS, Hoadley KA, Carey LA, Perou CM, Serody JS
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Clin Cancer Res. 2014 Jul;20(14):3818-29. Epub 2014 Jun 10.
 
PURPOSE: Lymphocytic infiltration of tumors predicts improved survival in patients with breast cancer. Previous studies have suggested that this survival benefit is confined predominantly to the basal-like subtype. Immune infiltration in ovarian tumors is also associated with improved prognosis. Currently, it is unclear what aspects of the immune response mediate this improved outcome.
EXPERIMENTAL DESIGN: Using The Cancer Genome Atlas mRNA-seq data and a large microarray dataset, we evaluated adaptive immune gene expression by genomic subtype in breast and ovarian cancer. To investigate B-cells observed to be prognostic within specific subtypes, we developed methods to analyze B-cell population diversity and degree of somatic hypermutation (SHM) from B-cell receptor (BCR) sequences in mRNA-seq data.
RESULTS: Improved metastasis-free/progression-free survival was correlated with B-cell gene expression signatures, which were restricted mainly to the basal-like and HER2-enriched breast cancer subtypes and the immunoreactive ovarian cancersubtype. Consistent with a restricted epitope-driven response, a subset of basal-like and HER2-enriched breast tumors and immunoreactive ovarian tumors showed high expression of a low-diversity population of BCR gene segments. More BCR segments showed improved prognosis with increased expression in basal-like breast tumors and immunoreactive ovarian tumors compared with other subtypes. Basal-like and HER2-enriched tumors exhibited more BCR sequence variants in regions consistent with SHM.
CONCLUSION: Taken together, these data suggest the presence of a productive and potentially restricted antitumor B-cell response in basal-like breast and immunoreactive ovarian cancers. Immunomodulatory therapies that support B-cell responses may be a promising therapeutic approach to targeting these B-cell infiltrated tumors.
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Authors' Affiliations: Lineberger Comprehensive Cancer Center; Curriculum in Genetics and Molecular Biology; Departments of.
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