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Journal of Clinical Oncology, Vol 19, Issue 5 (March), 2001: 1468-1475
© 2001 American Society for Clinical Oncology

Comparative Analysis of Micrometastasis to the Bone Marrow and Lymph Nodes of Node-Negative Breast Cancer Patients Receiving No Adjuvant Therapy

By Stephan Braun, B. Semeni Cevatli, Cyamak Assemi, Wolfgang Janni, Christina R.M. Kentenich, Christian Schindlbeck, Dorothea Rjosk, Florian Hepp

From the I. Frauenklinik and Department of Gynecological Pathology, Klinikum Innenstadt, Ludwig-Maximilians-University, München; Germany.

Address reprint requests to Stephan Braun, MD, Frauenklinik & Poliklinik, Klinikum rechts der Isar, Technical Universität, Ismaninger Strasse 22, D-81675 Munich, Germany; email: stephan.braun{at}lrz.tum.de

PURPOSE: In node-negative patients, of whom up to 30% will recur within 5 years after diagnosis, markers are still needed that identify patients at high enough risk to warrant further adjuvant treatment. In the present study we analyzed whether a correlation exists between microscopic tumor cell spread to bone marrow and to lymph nodes and attempted to determine which route is clinically more important.

PATIENTS AND METHODS: According to a prospective design, bone marrow aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative patients with stage I or II breast cancer were analyzed immunocytochemically with monoclonal anticytokeratin (CK) antibodies. We investigated associations with prognostic factors and the effect of micrometastasis on patients’ prognosis.

RESULTS: CK-positive cells in bone marrow aspirates were present in 44 (29%) of 150 breast cancer patients, whereas only 13 patients (9%) had such positive findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph nodes was seen in merely two patients. No correlation of bone marrow micrometastases with other risk factors was assessed. Reduced 4-year distant disease-free and overall survival were each associated with a positive bone marrow finding (P = .032 and P = .014, respectively) but not with lymph node micrometastasis. Multivariate analysis revealed an independent prognostic effect of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95% confidence interval, 1.2 to 31.3) for cancer-related death (P = .031) in our series.

CONCLUSION: Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.




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