title: Copy number imbalances between screen- and symptom-detected breast cancers and impact on disease-free survival.
abstract: Screening mammography results in the increased detection of indolent tumors. We hypothesized that screen- and symptom-detected tumors would show genotypic differences as copy number imbalances (CNI) that, in part, explain differences in the clinical behavior between screen- and symptom-detected breast tumors. We evaluated 850 women aged 40 and above diagnosed with stage I and II breast cancer at the University of Texas MD Anderson Cancer Center between 1985 and 2000 with information available on method of tumor detection (screen vs. symptoms). CNIs in screen- and symptom-detected tumors were identified using high-density molecular inversion probe arrays. Cox proportional modeling was used to estimate the effect of method of tumor detection on disease-free survival after adjusting for age, stage, and the CNIs. The majority of tumors were symptom detected (n = 603) compared with screen detected (n = 247). Copy number gains in chromosomes 2p, 3q, 8q, 11p, and 20q were associated with method of breast cancer detection (P < 0.00001). We estimated that 32% and 63% of the survival advantage of screen detection was accounted for by age, stage, nuclear grade, and Ki67 in women aged 50 to 70 and aged 40 to 87, respectively. In each age category, an additional 20% of the survival advantage was accounted for by CNIs associated with method of detection. Specific CNIs differ between screen- and symptom-detected tumors and explain part of the survival advantage associated with screen-detected tumors. Measurement of tumor genotype has the potential to improve discrimination between indolent and aggressive screen-detected tumors and aids patient and physician decision making about use of surgical and adjuvant treatments.
authors.affiliation: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, 77230, USA. abrewster@mdanderson.org
authors.forename: A M
authors.initials: AM
authors.lastname: Brewster
authors.forename: P
authors.initials: P
authors.lastname: Thompson
authors.forename: A A
authors.initials: AA
authors.lastname: Sahin
authors.forename: K
authors.initials: K
authors.lastname: Do
authors.forename: M
authors.initials: M
authors.lastname: Edgerton
authors.forename: J L
authors.initials: JL
authors.lastname: Murray
authors.forename: S
authors.initials: S
authors.lastname: Tsavachidis
authors.forename: R
authors.initials: R
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Mills
authors.forename: M
authors.initials: M
authors.lastname: Bondy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D018572:Disease-Free Survival; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D060787:Neoplasm Grading; D012189:Retrospective Studies; D015996:Survival Rate