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

Title: The presence of disseminated tumour cells in the bone marrow is inversely related to circulating free DNA in plasma in breast cancer dormancy
Authors: Payne, RE
Hava, NL
Page, K
Blighe, K
Ward, B
Slade, M
Brown, J
Guttery, DS
Zaidi, SAA
Stebbing, J
Jacob, J
Yaguee, E
Shaw, JA
Coombes, RC
Item Type: Journal Article
Abstract: 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.
Issue Date: 17-Jan-2012
Date of Acceptance: 10-Nov-2011
URI: http://hdl.handle.net/10044/1/97517
DOI: 10.1038/bjc.2011.537
ISSN: 0007-0920
Publisher: Springer Nature [academic journals on nature.com]
Start Page: 375
End Page: 382
Journal / Book Title: British Journal of Cancer
Volume: 106
Issue: 2
Copyright Statement: © 2012 Cancer Research UKFrom twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Sponsor/Funder: National Institute for Health Research
Cancer Research UK
Action Against Cancer
Action Against Cancer
Action Against Cancer
Action Against Cancer
Action Against Cancer
Medical Research Council (MRC)
Action Against Cancer
Medical Research Council (MRC)
Action Against Cancer
Breast Cancer Care & Breast Cancer Now
Action Against Cancer
Action Against Cancer
Cancer Research UK
Eisai Europe Ltd
Action Against Cancer
Imperial College Trust
Imperial College Healthcare NHS Trust- BRC Funding
Action Against Cancer
Action Against Cancer
Action Against Cancer
Action Against Cancer
Pink Ribbon Foundation
Imperial College Trust
Worldwide Cancer Research
Imperial College Trust
Imperial College Healthcare Charity
Breast Cancer Care & Breast Cancer Now
Imperial College Trust
Breast Cancer Research Trust
Funder's Grant Number: NIHR-RP-011-053
14549
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Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
circulating tumour cells
disseminated tumour cells
circulating-free DNA
dormancy
breast cancer
POLYMERASE-CHAIN-REACTION
ADJUVANT THERAPY
BLOOD-PLASMA
MICROMETASTASES
SERUM
QUANTIFICATION
INTEGRITY
APOPTOSIS
Bone Marrow
Breast Neoplasms
Case-Control Studies
DNA
Female
Follow-Up Studies
Genes, erbB-2
Humans
Immunohistochemistry
Polymerase Chain Reaction
Receptors, Estrogen
Bone Marrow
Humans
Breast Neoplasms
Receptors, Estrogen
DNA
Immunohistochemistry
Case-Control Studies
Follow-Up Studies
Polymerase Chain Reaction
Genes, erbB-2
Female
Science & Technology
Life Sciences & Biomedicine
Oncology
circulating tumour cells
disseminated tumour cells
circulating-free DNA
dormancy
breast cancer
POLYMERASE-CHAIN-REACTION
ADJUVANT THERAPY
BLOOD-PLASMA
MICROMETASTASES
SERUM
QUANTIFICATION
INTEGRITY
APOPTOSIS
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1117 Public Health and Health Services
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine