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• W3130624271 abstract "Abstract Background: Male breast cancer (MaBC) is rare, comprising &lt;1% of all breast cancers in the United States. The low incidence of MaBC limits the ability to conduct clinical trials specifically for this population. Due to the paucity of research on MaBC, current understanding regarding MaBC biology, pathology, and treatment strategies has been primarily based on evidence extrapolated from research on female breast cancer (FBC) patients. Traditional diagnostic biomarkers such as ER, PR, and HER2, as well as newer multi-gene prognostic signatures, are employed when making treatment decisions for both MaBC and FBC. However, limited empirical data is available to support the use of identical laboratory biomarkers and molecular signatures in both MaBC and FBC. The 70-gene risk of distant recurrence signature, MammaPrint (MP), and the 80-gene molecular subtyping signature, BluePrint (BP), are commonly used to help make treatment decisions for both MaBC and FBC patients. To support the clinical utility of MP and BP in MaBC, this study aims to elucidate whether significant molecular biological differences exist between MaBC and FBC. To address this knowledge gap, we evaluated and compared 1) MP index results within Low Risk (LR) and High Risk (HR) groups, 2) MP and BP gene expression, and 3) differentially expressed genes within the full genome and their associated biological pathways between tumors from MaBC and FBC. Methods: This analysis included a total of 817 breast tumor samples sent to Agendia, Inc. (Irvine, CA) for MP and BP testing. Full-transcriptome microarray data were available for 1) a subset of 400 post-menopausal FBC patients enrolled in the FLEX Registry (NCT03053193) and 2) 80 MaBC pateints, 32 of whom enrolled in the FLEX registry and 48 non-study patients for whom data were limited to metadata and quality metrics routinely captured for diagnostic testing. Data from all patients were de-indentified. Differences in mean MP indices between FBC (N=400) and MaBC (N=417) according to MP Risk classification (LR or HR) were analyzed using a Z-test. Differential gene expression analysis was performed using the R-limma package in which gene expression data were quantile normalized. Pathway analyses were performed using GOseq. Differentially expressed genes (DEGs) were identified between FBC (N=400) and MaBC (N=80) for whom full transcriptome microarray data were available. DEGs were defined as those with a fold change of &gt; 2 and an adjusted P value of &lt; 0.05. Results: All patients in this study had hormone positive, HER2 negative early-stage breast cancer. There was no statistical difference in the average MP index between MaBC and FBC classified as MP LR (P=0.273) or those classified as MP HR (P=0.692). Gene expression comparison revealed 166 DEGs between MaBC (N=80) and FBC (N=400), 99 DEGs between MP HR MaBC (N=42) and MP HR FBC (N=200), and 290 DEGs between MP LR MaBC (N=38) and MP LR FBC (N=200). Pathway analyses revealed that downregulated genes in MaBC compared to FBC enriched to immune-related functions, including B-cell mediated immunity, whereas upregulated genes were associated with hormone metabolic processes. In all comparisons, expression of MP or BP genes was not significantly different. Conclusions: We found similar MP index distributions between MaBC and FBC. Importantly, differential gene expression between MaBC and FBC provides novel insight into the mechanisms underlying MaBC. Although these data reveal biological distinctions between male and female breast cancer, MP and BP assay performance is preserved across both groups. Further studies are needed to assess clinical outcomes; however, these findings support the use of MP risk of recurrence assay and BP molecular subtyping assay for prognosis and informing treatment decisions in MaBC. Citation Format: Jennifer Crozier, Julie Barone, Kalyan Banda, Beth Lesnikoski, Robert Maganini, Sami Diab, Ian Grady, Thomas Lomis, Charles Cox, Amy Truitt, Benjamin Nota, Andrea Menicucci, Erin Yoder, William Audeh, FLEX Investigators Group. Differential gene expression analysis and clinical utility of MammaPrint and BluePrint in male breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-11." @default.
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• W3130624271 date "2021-02-15" @default.
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• W3130624271 title "Abstract PS14-11: Differential gene expression analysis and clinical utility of MammaPrint and BluePrint in male breast cancer patients" @default.
• W3130624271 doi "https://doi.org/10.1158/1538-7445.sabcs20-ps14-11" @default.
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