Introduction: Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). Methods: In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples. Results and discussion: A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.

Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology / Valentini, Virginia; Silvestri, Valentina; Bucalo, Agostino; Conti, Giulia; Karimi, Mina; Di Francesco, Linda; Pomati, Giulia; Mezi, Silvia; Cerbelli, Bruna; Pignataro, Maria Gemma; Nicolussi, Arianna; Coppa, Anna; D’Amati, Giulia; Giannini, Giuseppe; Ottini, Laura. - In: FRONTIERS IN ONCOLOGY. - ISSN 2234-943X. - 12:(2023). [10.3389/fonc.2022.1092201]

Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology

Valentini, Virginia
Primo
;
Silvestri, Valentina
Secondo
;
Bucalo, Agostino;Conti, Giulia;Karimi, Mina;Di Francesco, Linda;Pomati, Giulia;Mezi, Silvia;Cerbelli, Bruna;Pignataro, Maria Gemma;Nicolussi, Arianna;Coppa, Anna;D’Amati, Giulia;Giannini, Giuseppe
Penultimo
;
Ottini, Laura
Ultimo
2023

Abstract

Introduction: Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). Methods: In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples. Results and discussion: A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.
2023
male breast cancer (MBC), tumor profiling, targeted gene panel sequencing, clinically actionable genetic variants, tumor mutational burden (TMB), microsatellite instability (MSI), copy number variations (CNVs), precision oncology
01 Pubblicazione su rivista::01a Articolo in rivista
Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology / Valentini, Virginia; Silvestri, Valentina; Bucalo, Agostino; Conti, Giulia; Karimi, Mina; Di Francesco, Linda; Pomati, Giulia; Mezi, Silvia; Cerbelli, Bruna; Pignataro, Maria Gemma; Nicolussi, Arianna; Coppa, Anna; D’Amati, Giulia; Giannini, Giuseppe; Ottini, Laura. - In: FRONTIERS IN ONCOLOGY. - ISSN 2234-943X. - 12:(2023). [10.3389/fonc.2022.1092201]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1664405
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