Recurrence rates after breast-conserving
therapy may depend on genomic characteristics of
cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of
cancer-adjacent breast tissue. To estimate the prevalence of
DNA defects and
RNA expression subtypes in
cancer-adjacent, benign-appearing breast tissue at least 2 cm from the
tumor margin,
cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The
Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation,
messenger RNA (
mRNA) sequence, and
mRNA/
microRNA expression. Additional samples were also analyzed by at least one of these genomic data types and associations between genomic characteristics of normal tissue and overall survival were assessed. Approximately 40% of
cancer-adjacent, benign-appearing tissues harbored genomic defects in
DNA copy number, sequence, methylation, or in RNA sequence, although these defects did not significantly predict 10-year overall survival. Two
mRNA/
microRNA expression phenotypes were observed, including an active
mRNA subtype that was identified in 40% of samples. Controlling for
tumor characteristics and the presence of genomic defects, this active subtype was associated with significantly worse 10-year survival among
estrogen receptor (ER)-positive cases. This multi-platform analysis of
breast cancer-adjacent samples produced genomic findings consistent with current
surgical margin guidelines, and provides evidence that extratumoral
RNA expression patterns in
cancer-adjacent tissue predict overall survival among patients with ER-positive disease.