The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.
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Authors
Barry, P
Vatsiou, A
Spiteri, I
Nichol, D
Cresswell, GD
Acar, A
Trahearn, N
Hrebien, S
Garcia-Murillas, I
Chkhaidze, K
Ermini, L
Huntingford, IS
Cottom, H
Zabaglo, L
Koelble, K
Khalique, S
Rusby, JE
Muscara, F
Dowsett, M
Maley, CC
Natrajan, R
Yuan, Y
Schiavon, G
Turner, N
Sottoriva, A
Vatsiou, A
Spiteri, I
Nichol, D
Cresswell, GD
Acar, A
Trahearn, N
Hrebien, S
Garcia-Murillas, I
Chkhaidze, K
Ermini, L
Huntingford, IS
Cottom, H
Zabaglo, L
Koelble, K
Khalique, S
Rusby, JE
Muscara, F
Dowsett, M
Maley, CC
Natrajan, R
Yuan, Y
Schiavon, G
Turner, N
Sottoriva, A
Document Type
Journal Article
Date
2018-02-01
Date Accepted
2018-06-05
Abstract
Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localized and systemic disease is key to understanding breast cancer progression; however, our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data are derived from primary tumors.Experimental Design: In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multiregion sequencing (n = 78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumor DNA (ctDNA).Results: Linear evolution from primary to lymph node was rare (1/11), whereas the majority of cases displayed either early divergence between primary and nodes (4/11) or no detectable divergence (6/11), where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken perioperatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients. Clin Cancer Res; 24(19); 4763-70. ©2018 AACR.
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (19), pp. 4763 - 4770
Source Title
Publisher
SPRINGER
ISSN
1078-0432
eISSN
1557-3265
Collections
Research Team
Molecular Oncology
Computational Pathology & Integrated Genomics
Endocrinology
Evolutionary Genomics & Modelling
Functional Genomics
Computational Pathology & Integrated Genomics
Endocrinology
Evolutionary Genomics & Modelling
Functional Genomics