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Does Analysis of Biomarkers in Tumor Cells in Lymph Node Metastases Give Additional Prognostic Information in Primary Breast Cancer?

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Abstract

Background

Prognostic and treatment-predictive biomarkers in primary breast cancer are routinely analyzed in the primary tumor, whereas metastatic tumor cells in lymph node metastases are not characterized. The present study aimed to define the concordance between biomarkers in matched pairs of breast cancers and lymph node metastases and to relate their expression to clinical outcome.

Methods

Patients with primary breast cancer treated with adjuvant tamoxifen for 2 years were included. A tissue microarray of primary tumors and lymph node metastases was constructed, and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed immunohistochemically in 262, 257, 104, and 101 patients, respectively. Five years’ distant disease-free survival (DDFS) was used as the primary end point.

Results

The concordance for biomarker expression in primary tumors and corresponding lymph node metastases was 93% for ER, 84% for PR, 97% for HER2, and 85% for Ki67. The discordant cases for HER2 status were all negative in the tumor but positive in the node. ER positivity was a significant independent predictor of improved 5-year DDFS when analyzed in the primary tumor as well as in the lymph node metastases. Ki67 positivity analyzed in both locations correlated with shortened DDFS. HER2 positivity at both locations was an indicator of early relapse.

Conclusions

The concordance for the biomarkers analyzed in matched pairs of primary tumors and lymph node metastases was high. Moreover, survival analyses showed that the expression of biomarkers in lymph node metastases can provide prognostic information when no analyses of the primary tumor can be done. Treatment selection based on biomarkers in the lymph node is a topic for further studies.

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Acknowledgments

We are indebted to the participating departments of the South Sweden Breast Cancer Group for providing us with breast cancer samples and clinical follow-up data; to Kristina Lövgren for skilled technical assistance with preparation of the tissue microarray, staining procedures, and examination of the slides; and to Janica Kallonen for examination of the slides. The study was supported by funds from the medical faculty and University Hospital Lund (ALF), The University Hospital of Lund Research Foundation, the Swedish Pink Ribbon Campaign, and Skåne County Council’s research and development Foundation.

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Authors and Affiliations

  1. Department of Surgery, Institution of Clinical Sciences Lund, Lund University Hospital, SE-221 85, Lund, Sweden

    Anna-Karin Falck & Lisa Rydén

  2. Department of Oncology, Institution of Clinical Sciences Lund, Lund University Hospital, SE-221 85, Lund, Sweden

    Mårten Fernö & Pär-Ola Bendahl

Authors
  1. Anna-Karin Falck
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  2. Mårten Fernö
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  3. Pär-Ola Bendahl
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  4. Lisa Rydén
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Correspondence to Lisa Rydén.

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Falck, AK., Fernö, M., Bendahl, PO. et al. Does Analysis of Biomarkers in Tumor Cells in Lymph Node Metastases Give Additional Prognostic Information in Primary Breast Cancer?. World J Surg 34, 1434–1441 (2010). https://doi.org/10.1007/s00268-010-0499-z

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