title: Comparison of breast cancer to healthy control tissue discovers novel markers with potential for prognosis and early detection.
abstract: This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.
authors.affiliation: Molecular Diagnostics Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. mschumme@fhcrc.org
authors.forename: Michèl
authors.initials: M
authors.lastname: Schummer
authors.forename: Ann
authors.initials: A
authors.lastname: Green
authors.forename: J David
authors.initials: JD
authors.lastname: Beatty
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Karlan
authors.forename: Scott
authors.initials: S
authors.lastname: Karlan
authors.forename: Jenny
authors.initials: J
authors.lastname: Gross
authors.forename: Sean
authors.initials: S
authors.lastname: Thornton
authors.forename: Martin
authors.initials: M
authors.lastname: McIntosh
authors.forename: Nicole
authors.initials: N
authors.lastname: Urban
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016000:Cluster Analysis; D042241:Early Diagnosis; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor