Copy number variations (CNVs) encompass a variety of genetic alterations 
including deletions and amplifications and cluster in regions of the human 
genome with intrinsic instability. Small-sized CNVs can act as initial genetic 
changes giving rise to larger CNVs such as acquired somatic copy number 
aberrations (CNAs) promoting cancer formation. Previous studies provided 
evidence for CNVs as an underlying cause of elevated breast cancer risk when 
targeting breast cancer susceptibility genes and of accelerated breast cancer 
progression when targeting oncogenes. With the development of novel techniques 
for genome-wide detection of CNVs at increasingly higher resolution, it became 
possible to qualitatively and quantitatively analyse manifestation of DNA damage 
resulting from defects in any of the large variety of DNA double-strand break 
(DSB) repair mechanisms. Breast carcinogenesis, particularly in familial cases, 
has been linked with a defect in the homologous recombination (HR) pathway, 
which in turn switches damage removal towards alternative, more error-prone DSB 
repair pathways such as microhomology-mediated non-homologous end joining 
(mmNHEJ). Indeed, increased error-prone DSB repair activities were detected in 
peripheral blood lymphocytes from individuals with familial breast cancer risk 
independently of specific gene mutations. Intriguingly, sequence analysis of 
breakpoint regions revealed that the majority of genome aberrations found in 
breast cancer specimens are formed by mmNHEJ. Detection of pathway-specific 
error-prone DSB repair activities by functional testing was proposed to serve as 
biomarker for hereditary breast cancer risk and responsiveness to therapies 
targeting HR dysfunction. Identification of specific error-prone DSB repair 
mechanisms underlying CNAs and ultimately mammary tumour formation highlights 
potential targets for future breast cancer prevention regimens.