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Detection of Tumor-Specific Genetic Alterations in Bone Marrow from Early-Stage Breast Cancer Patients¹

Department of Molecular Oncology [B. T., S. S., D. S. B. H.], Joyce Eisenberg-Keefer Breast Center [B. T., A. E. G., N. M. H.], Skeletal Biology [F. R. S.], John Wayne Cancer Institute, Santa Monica, California 90404

Detection of genetic markers associated with early breast cancer may prove clinically relevant for identifying patients at increased risk for relapse. Loss of heterozygosity (LOH), a specific genetic aberration, commonly occurs during breast cancer initiation and metastasis. Early detection of tumor metastasis to bone marrow (BM) using conventional histochemical techniques has been limited because of suboptimal efficiency and sensitivity. Because bone is such a common site of breast cancer recurrence, we sought to determine whether microsatellite markers associated with breast cancer could be detected in BM aspirates from patients with early-stage breast cancer. Cell-free plasma from BM aspirates in 48 patients was assessed for LOH using a panel of eight polymorphic microsatellite markers. LOH was detected in 11 (23%) of 48 patients’ BM aspirates. Advancing American Joint Committee on Cancer (AJCC) stage was associated with an increased incidence of LOH. Concordance was present between LOH identified in BM aspirates and matched-pair primary tumors. No samples contained detectable tumor cells on routine histology. In 24 patients, paired peripheral blood serum samples were available for analysis. In these cases, BM detection of LOH was more frequent than serum. This study demonstrates the novel finding of tumor-related genetic markers in BM aspirate plasma of early-stage breast cancer patients and provides a unique approach for assessing subclinical systemic disease progression and the monitoring of breast cancer patients.

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