The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.
Date
2018-02-01ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Axilla
Lymph Nodes
Humans
Breast Neoplasms
Lymphatic Metastasis
Neoplasm Proteins
Neoplasm Staging
Gene Expression Regulation, Neoplastic
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Clonal Evolution
Circulating Tumor DNA
Research team
Molecular Oncology
Computational Pathology & Integrated Genomics
Endocrinology
Evolutionary Genomics & Modelling
Functional Genomics
Language
eng
Date accepted
2018-06-05
License start date
2018-10
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (19), pp. 4763 - 4770
Publisher
SPRINGER