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Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases.

Carlsson, Anders LU ; Wingren, Christer LU ; Nordström, Malin LU ; Rose, Carsten LU ; Fernö, Mårten LU ; Olsson, Håkan LU ; Jernstöm, Helena; Ek, Sara LU ; Gustavsson, Elin LU and Ingvar, Christian LU , et al. (2011) In Proceedings of the National Academy of Sciences 108(34). p.14252-14257
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... (More)
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. (Less)
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Proceedings of the National Academy of Sciences
volume
108
issue
34
pages
14252 - 14257
publisher
National Acad Sciences
external identifiers
  • wos:000294163500076
  • pmid:21844363
  • scopus:80052142418
ISSN
1091-6490
DOI
10.1073/pnas.1103125108
project
CREATE Health
language
English
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yes
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4ef097ac-ddc3-4e44-95b0-4c443eeee534 (old id 2151027)
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http://www.ncbi.nlm.nih.gov/pubmed/21844363?dopt=Abstract
date added to LUP
2011-09-04 14:58:03
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2017-09-10 04:42:52
@article{4ef097ac-ddc3-4e44-95b0-4c443eeee534,
  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.},
  author       = {Carlsson, Anders and Wingren, Christer and Nordström, Malin and Rose, Carsten and Fernö, Mårten and Olsson, Håkan and Jernstöm, Helena and Ek, Sara and Gustavsson, Elin and Ingvar, Christian and Ohlsson, Mattias and Peterson, Carsten and Borrebaeck, Carl},
  issn         = {1091-6490},
  language     = {eng},
  number       = {34},
  pages        = {14252--14257},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases.},
  url          = {http://dx.doi.org/10.1073/pnas.1103125108},
  volume       = {108},
  year         = {2011},
}