title: Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases.
abstract: The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into high- versus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.
authors.affiliation: Department of Immunotechnology, CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Carlsson
authors.forename: Christer
authors.initials: C
authors.lastname: Wingren
authors.forename: Malin
authors.initials: M
authors.lastname: Kristensson
authors.forename: Carsten
authors.initials: C
authors.lastname: Rose
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
authors.forename: Sara
authors.initials: S
authors.lastname: Ek
authors.forename: Elin
authors.initials: E
authors.lastname: Gustavsson
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.forename: Mattias
authors.initials: M
authors.lastname: Ohlsson
authors.forename: Carsten
authors.initials: C
authors.lastname: Peterson
authors.forename: Carl A K
authors.initials: CA
authors.lastname: Borrebaeck
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003710:Demography; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012008:Recurrence; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor