Novel gene variants identified in male breast cancer

Male breast cancer (MBC) is a very rare tumor type, occurring in just 1% of all breast cancer cases, and the underlying genetic causes and treatment of MBC is not well understood. In a paper published in the March issue of Cold Spring Harbor Molecular Case Studies, researchers from Italy and the U.S. describe novel genetic variants found in a hormone receptor positive (HR+) MBC patient, that are distinct from previously identified genetic variants found in ten MBC cases.

The authors present the treatment history of a HR+ male breast cancer patient. His disease stabilized from targeting of the PI3K/mTOR pathway using the PI3K/mTOR inhibitor BEZ235 in combination with everolimus as 3rd line treatment for his metastatic ductal carcinoma and experienced a prolonged stable disease. After 18 months he subsequently became resistant to the treatment and his disease progressed. The authors then investigated why the patient benefited and subsequently developed resistance to this combination treatment using genomic and immunohistochemical analysis.

Whole-exome sequencing was performed on pre-treatment and post-progression samples of the MBC patient, as compared to a whole blood normal control. The researchers found that a region of Chromosome 12p was deleted in the resistant tumor and that HR protein expression was increased in the resistant tumor.

This research provides new insights into both male breast cancer and response to BEZ235/everolimus combination treatment. This study adds to our understanding of MBC development and resistance, and the authors commented that “”Breast cancer in men is a very rare disease, representing less than 1% of all breast cancer cases. So, very few and small studies have been conducted in this disease. Our analyses contributed to delineate the genomic landscape of male breast cancer and suggested a potential particular benefit in this disease by the combined treatment with Afinitor plus BEZ235 in order to achieve a complete blockade of the PI3K/Akt/mTOR pathway. “


Researchers from Verona University, Azienda Ospedaliera Universitaria Integrata, Novartis, Genoptix, contributed to this study.

Novel gene variants identified in male breast cancer This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) Start-Up n°10129, and 5 per mille n°10016 grants.

Media Contacts:

The authors are available for more information by contacting: Dr. Davide Melisi (.(JavaScript must be enabled to view this email address))

Interested reporters may obtain copies of the manuscript online at: or via email from Peggy Calicchia, Administrative Assistant (.(JavaScript must be enabled to view this email address), +1-516-422-4012)

About the article:

The manuscript will appear in the March issue of CSH Molecular Case Studies. Its full citation is: Molecular analysis of a male breast cancer patient with prolonged stable disease under mTOR/PI3K inhibitors BEZ235/everolimus A. Rose Brannon, Melissa Frizziero, David Chen, Jennifer Hummel,Jorge Gallo, Markus Riester, Parul Patel, Wing Cheung, Michael Morrissey,Carmine Carbone,Silvia Cottini, Giampaolo Tortora, and Davide Melisi Cold Spring Harb Mol Case Stud March 2016, 2: a000620

About Cold Spring Harbor Molecular Case Studies:

Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal’s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public.


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