The presence of disseminated tumour cells in the bone marrow is inversely related to circulating free DNA in plasma in breast cancer dormancy

• Published in: British journal of cancer Vol. 106; no. 2; pp. 375 - 382
• Main Authors: Payne, R E, Hava, N L, Page, K, Blighe, K, Ward, B, Slade, M, Brown, J, Guttery, D S, Zaidi, S A A, Stebbing, J, Jacob, J, Yagüe, E, Shaw, J A, Coombes, R C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.01.2012; Nature Publishing Group
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bone marrow; Bone Marrow - pathology; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer Research; Case-Control Studies; Cell death; Cytokeratin; Diseases of the osteoarticular system; DNA - blood; Drug Resistance; Epidemiology; Female; Follow-Up Studies; Genes, erbB-2; Humans; Immunohistochemistry; Medical prognosis; Medical research; Medical sciences; Metastasis; Molecular Diagnostics; Molecular Medicine; Oncology; Patients; Polymerase Chain Reaction; Receptors, Estrogen - metabolism; Surgery; Tumors; Tumors of striated muscle and skeleton; United Kingdom > UK; circulating-free DNA; disseminated tumour cells; circulating tumour cells; breast cancer; dormancy; Breast disease; Diseases of the osteoarticular system; Breast cancer; Malignant tumor; Blood plasma; Dormancy; Mammary gland diseases; Cancerology; Bone tumor; DNA; Disseminated; Tumor cell; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.537

Background: The aim of this study was to gain insight into breast cancer dormancy by examining different measures of minimal residual disease (MRD) over time in relation to known prognostic factors. Methods: Sixty-four primary breast cancer patients on follow-up (a median of 8.3 years post surgery) who were disease free had sequential bone marrow aspirates and blood samples taken for the measurement of disseminated tumour cells (DTCs), circulating tumour cells (CTCs) by CellSearch and qPCR measurement of overlapping (96-bp and 291-bp) amplicons in circulating free DNA (cfDNA). Results: The presence of CTCs was correlated with the presence of DTCs measured by immunocytochemistry ( P =0.01) but both were infrequently detected. Increasing cfDNA concentration correlated with ER, HER2 and triple-negative tumours and high tumour grade, and the 291-bp amplicon was inversely correlated with DTCs measured by CK19 qRT-PCR ( P =0.047). Conclusion: Our results show that breast cancer patients have evidence of MRD for many years after diagnosis despite there being no overt evidence of disease. The inverse relationship between bone marrow CK19 mRNA and the 291-bp amplicon in cfDNA suggests that an inverse relationship between a measure of cell viability in the bone marrow (DTCs) and cell death in the plasma occurs during the dormancy phase of breast cancer.