Molecular Characterization of Male Breast Cancer
Abstract: Cancer is today a major healthcare problem worldwide. There are many forms of cancer, which is a genetic disease, believed to result from a multistep process with genetic and epigenetic changes accumulating over time. Breast cancer is one of the most common forms of cancer in women, while it is much more rare in men. Male breast cancer (MBC) exhibits both similarities and differences with female breast cancer (FBC). However, in contrast to FBC, MBC is poorly characterized on the molecular level. Multiple global profiling studies of FBC have been performed on the genetic and epigenetic levels, while only a few genetic studies have been performed on MBC. The aim of the research presented in this thesis was to study MBC on the genomic, transcriptomic and epigenomic levels, in an attempt to reveal some of the mechanisms of tumorigenesis in MBC, and to provide a detailed molecular landscape of the disease, allowing comparisons with FBC. The various studies were carried out using high-resolution microarrays and immunohistochemistry on a well-annotated cohort of MBC patients from whom 83 fresh frozen and 220 formalin-fixed paraffin-embedded samples were available. It was found that MBC is heterogeneous on a genomic, transciptomic and epigenetic level, consisting of various kinds of tumors, each of which exhibits its own aberrations, as is the case in FBC. Male and female breast cancer tumors had a similar appearance on a global level, but when studied in greater detail, many genetic and epigenetic differences were revealed. Furthermore, the landscapes of candidate drivers in male and female breast cancer appear to show considerable differences. Attempts were made to subclassify the fresh frozen MBC tumors with regard to copy number, and levels of mRNA and DNA methylation. Two stable subgroups were consistently identified, showing differences in the biological features of the tumors, where one of the subgroups seemed to consist of a number of more aggressive MBC tumors. The subgroups from the three datasets analyzed were significantly associated with each other, however, they differed from the known subgroups of FBC. As such, they may constitute two novel subgroups of breast cancer, occurring exclusively in men. This indicates that breast cancer in men may require different management and treatment strategies from those used in women with breast cancer.
CLICK HERE TO DOWNLOAD THE WHOLE DISSERTATION. (in PDF format)