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The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.

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.

SUBMITTER: Barry P

PROVIDER: S-EPMC6296441 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.

Barry Peter P Vatsiou Alexandra A Spiteri Inmaculada I Nichol Daniel D Cresswell George D GD Acar Ahmet A Trahearn Nicholas N Hrebien Sarah S Garcia-Murillas Isaac I Chkhaidze Kate K Ermini Luca L Huntingford Ian Said IS Cottom Hannah H Zabaglo Lila L Koelble Konrad K Khalique Saira S Rusby Jennifer E JE Muscara Francesca F Dowsett Mitch M Maley Carlo C CC Natrajan Rachael R Yuan Yinyin Y Schiavon Gaia G Turner Nicholas N Sottoriva Andrea A

Clinical cancer research : an official journal of the American Association for Cancer Research 20180611 19

<b>Purpose:</b> 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.<b>Experimental Design:</b> In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant meta ...[more]

PMID: 29891724

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Project description:Purpose:Axillary lymph node (ALN) involvement is an important prognostic factor of early invasive breast cancer. The objective of this study was to establish simple nomograms for predicting ALN involvement based on ultrasound (US) characteristics and evaluate the predictive value of US in the detection of ALN involvement. Patients and Methods:A total of 1328 patients with cT1-2N0 breast cancer by physical exam were retrospectively analyzed. Univariate analysis was used for the comparison of variables, and multivariate analysis was performed by binary logistic regression analysis. The R software was used to establish simple nomograms based on the US characteristics alone. The receiver operating characteristic (ROC) curves of the prediction model and the verification group were drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of the prediction model. A calibration curve was plotted to assess the nomogram predictions vs the actual observations of the ALN metastasis rate and axillary tumor burden rate. Results:The ALN metastasis rates of the training group and the validation group were 35.1% and 34.1%, respectively. Multivariate analysis showed that molecular subtype, lymphovascular invasion, mass descriptors (size, margin, microcalcification and blood flow signal) and LN descriptors (shape, cortical thickness and long-to-short ratio) were independent impact factors in early breast cancer. The AUC of ALN metastasis rate of prediction model based on US features was 0.802, the AUC of high tumor burden rate was 0.873, and the AUC of external validation group was 0.731 and 0.802, respectively. The calibration curve of the nomogram showed that the nomogram predictions are consistent with the actual metastasis rate and the high tumor burden rate. The results showed that preoperative US had a sensitivity of 59.4% and a specificity of 88.9% for predicting the ALN metastasis rate. Conclusion:The successfully established nomograms based on US characteristics to predict ALN metastasis rate and high axillary tumor burden rate in early breast cancer can achieve individual prediction. Compared with other nomogram predictions, it is more intuitive, and can help clinical decision-making; thus, it should be promoted. However, at this time US features alone are insufficient to replace sentinel lymph node biopsy.

Dataset Information

The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.

Publications

The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.

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