American Association for Cancer Research
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Figure S3 from Prediction of Lymph Node Metastasis in Breast Cancer by Gene Expression and Clinicopathological Models: Development and Validation within a Population-Based Cohort

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journal contribution
posted on 2023-03-31, 21:04 authored by Looket Dihge, Johan Vallon-Christersson, Cecilia Hegardt, Lao H. Saal, Jari Häkkinen, Christer Larsson, Anna Ehinger, Niklas Loman, Martin Malmberg, Pär-Ola Bendahl, Åke Borg, Johan Staaf, Lisa Rydén

Cohen's kappa coefficient displaying the degree of inter-model agreement and barplots displaying percentage of correctly predicted cases by the derived models versus clinical N0, N1, N2 status across evaluation groups


Swedish Cancer Society

Skåne County Council's Research and Development Foundation


The Swedish Breast Cancer Association

Mrs. Berta Kamprad Foundation

Crafoord Foundation

Erling-Persson Family Foundation



More than 70% of patients with breast cancer present with node-negative disease, yet all undergo surgical axillary staging. We aimed to define predictors of nodal metastasis using clinicopathological characteristics (CLINICAL), gene expression data (GEX), and mixed features (MIXED) and to identify patients at low risk of metastasis who might be spared sentinel lymph node biopsy (SLNB).Experimental Design: Breast tumors (n = 3,023) from the population-based Sweden Cancerome Analysis Network–Breast initiative were profiled by RNA sequencing and linked to clinicopathologic characteristics. Seven machine-learning models present the discriminative ability of N0/N+ in development (n = 2,278) and independent validation cohorts (n = 745) stratified as ER+HER2−, HER2+, and TNBC. Possible SLNB reduction rates are proposed by applying CLINICAL and MIXED predictors. In the validation cohort, the MIXED predictor showed the highest area under ROC curves to assess nodal metastasis; AUC = 0.72. For the subgroups, the AUCs for MIXED, CLINICAL, and GEX predictors ranged from 0.66 to 0.72, 0.65 to 0.73, and 0.58 to 0.67, respectively. Enriched proliferation metagene and luminal B features were noticed in node-positive ER+HER2− and HER2+ tumors, while upregulated basal-like features were observed in node-negative TNBC tumors. The SLNB reduction rates in patients with ER+HER2− tumors were 6% to 7% higher for the MIXED predictor compared with the CLINICAL predictor accepting false negative rates of 5% to 10%. Although CLINICAL and MIXED predictors of nodal metastasis had comparable accuracy, the MIXED predictor identified more node-negative patients. This translational approach holds promise for development of classifiers to reduce the rates of SLNB for patients at low risk of nodal involvement.