Anders Carlsson, Christer Wingren, Malin Kristensson, Carsten Rose, Mårten Fernö, Håkan Olsson, Helena Jernström, Sara Ek, Elin Gustavsson, Christian Ingvar, Mattias Ohlsson, Carsten Peterson and Carl A.K. Borrebaeck
Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases
Proceedings of the National Academy of Sciences USA 108, 14252-14257 (2011)

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 months after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then after 3-6 months. 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 subsequently tested, and evaluated in an independent test cohort (pre-validation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using their molecular portraits. The results from this pre-validation study showed that a classification of patients into high vs. low risk for developing metastatic breast cancer could be performed with an area under the ROC curve (AUC) 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 to conventional clinical parameters. Consequently, we have demonstrated the first candidate, serum biomarker signature able to classify patients with primary breast cancer regarding the risk of developing distant recurrence, with an accuracy outperforming current procedures.

LU TP 10-09