The Micrometastasis group has focused on development, testing and standardization of methods for detection and characterisation of DTC and CTC, in addition to running large clinical trials. A better treatment of patients with breast cancer needs improved assessment of the individual risk of harboring minimal residual disease after completion of the surgical treatment. This includes improved risk classification, sub-classification of the breast cancer disease and identification of high risk patients that do not respond to the standard chemo- and/or hormonal therapy, who are candidates for more aggressive/alternative treatment. The breast cancer micrometastasis projects approach these issues by – primary tumor analyses for selection of clinically relevant genes and gene-products, and by detection and characterization of disseminated tumor cells (DCTs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood. Several characterisation techniques are established (array CGH/genome sequencing, FISH, immunofluorescence). Large patient cohorts with both primary tumor, blood and bone marrow available are studied, including a population of 920 breast cancer patients (Oslo1 study) with known clinical outcome status, as well as new studies (Oslo2, Neo-AVA, SATT study, I-BCT, ALICE). The detection and analysis of CTCs includes use of new promising techniques (CellSearch and quantitative RT-PCR. In a different study of 1120 patients receiving standard chemotherapy after primary surgery (SATT study), BM analysis has been performed after completion of standard chemotherapy for detection and characterization of remaining tumor cells. If present, the patients receive additional chemotherapy of a different type (docetaxel), followed by further monitoring of BM for DTCs. The tumor- and recurrence status of patients with persistence and disappearance of DTCs in bone marrow cells will be compared (ongoing work), to predict the effect of the chemotherapy and to disclose the value of the DTC analysis as a surrogate marker for treatment response. The micrometastasis group has now established the nCounter system (Nanostring) in the laboratory,  to be used for molecular (DNA and RNA) analyses of both formalin-fixed primary tumor tissue from the patients as well as for additional future single cell analyses. Currently, the PAM50 ROR analysis (Prosigna test) is run on primary tumor samples from patients within studies in the research network (EMIT study). 

PI Bjørn Naume, MD PhD, Co-PI of the network. Oslo University Hospital. Photo: Studio E.

Selected papers:

• Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer. Naume et al. J Clin Oncol. 2014.
• Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse – a European pooled analysis. Janni et al. Clin Cancer Res. 2011.
• Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing. Demeulemeester, Kumar, Møller et al. Genome Biol. 2016
• Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival. Mathiesen et al. Breast Cancer Res. 2012
• A pooled analysis of bone marrow micrometastasis in breast cancer. Braun et al. N Engl J Med. 2005.

Group members:

• Bjørn Naume, MD, PhD. Email: bna(at)ous-hf.no
• Elin Borgen, MD PhD.
• Hege Russnes, MD PhD.
• Anne Renolen, MSc.
• Cecilie Schirmer.
• Maria Rypdal.
• Marit Aaserud, MSc.
• My Anh Tu Sveli, MSc.
• Ingrid Øverlie Bakka, MSc.
• Sara Kristine Hverven, MSc.