title: High-resolution genomic profiling to predict 10-year overall survival in node-negative breast cancer.
abstract: Women with clinically node-negative breast cancer have a better prognosis than do those with axillary lymph node metastasis. Nonetheless, approximately 20% of node-negative patients die within 15 years of diagnosis, and thus additional prognostic markers are greatly needed. To identify specific copy number alterations (CNAs) that differed in frequency between 10-year survivors and deceased patients with node-negative breast cancer, array comparative genomic hybridization (aCGH) was applied to 41 primary node-negative breast tumors. Fisher's exact test was used to identify significantly different CNAs between 10-year survivors and deceased patients. Losses at 8p21.2 approximately p21.3, 8p23.1 approximately p23.2, Xp21.3, and Xp22.31 approximately p22.33 were significantly more common in tumors from deceased patients, suggesting that these alterations may contribute to tumor aggressiveness. Gains at 1q25.2 approximately q25.3 and 1q31.3 approximately q41 were more prevalent in tumors from survivors; specific gains at these genomic regions may inhibit further tumor progression, resulting in a less aggressive form of node-negative breast cancer. Evaluation of the identified CNAs in an independent external data set verified the prognostic potential of the 1q31.3 approximately q41 region. Although further extensive validation is needed, the prognostic CNAs identified in this work may in time facilitate the clinical assessment of breast cancer.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, University of Gothenburg, SE-413 45 Göteborg, Sweden. elin.karlsson@gu.se
authors.forename: Elin
authors.initials: E
authors.lastname: Möllerström
authors.forename: Ulla
authors.initials: U
authors.lastname: Delle
authors.forename: Anna
authors.initials: A
authors.lastname: Danielsson
authors.forename: Toshima
authors.initials: T
authors.lastname: Parris
authors.forename: Björn
authors.initials: B
authors.lastname: Olsson
authors.forename: Per
authors.initials: P
authors.lastname: Karlsson
authors.forename: Khalil
authors.initials: K
authors.lastname: Helou
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D002877:Chromosomes, Human; D055028:Comparative Genomic Hybridization; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis; D017741:Survivors; D013997:Time Factors