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Prediction of lymph node metastasis in breast cancer by gene expression and clinicopathological models: Development and validation within a population based cohort.

Dihge, Looket LU ; Vallon-Christersson, Johan LU ; Hegardt, Cecilia LU ; Saal, Lao LU ; Häkkinen, Jari LU ; Larsson, Christer LU ; Ehinger, Anna LU ; Loman, Niklas LU ; Malmberg, Martin LU and Bendahl, Pär-Ola LU , et al. (2019) In Clinical cancer research : an official journal of the American Association for Cancer Research 25(21). p.6368-6381
Abstract
Purpose: 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... (More)
Purpose: 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.

Results: 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%.

Conclusions: 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. (Less)
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Contribution to journal
publication status
published
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Clinical cancer research : an official journal of the American Association for Cancer Research
volume
25
issue
21
pages
6368 - 6381
publisher
American Association for Cancer Research
external identifiers
  • scopus:85074445110
  • pmid:31340938
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-19-0075
project
Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
Genomisk karakterisering av trippelnegativ bröstcancer (TNBC)
language
English
LU publication?
yes
id
ad7c8607-b5f5-4d54-b4c1-bf430615821c
date added to LUP
2019-08-21 13:11:21
date last changed
2020-01-13 02:17:24
@article{ad7c8607-b5f5-4d54-b4c1-bf430615821c,
  abstract     = {Purpose: 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).<br/><br/>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.<br/><br/>Results: 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%.<br/><br/>Conclusions: 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.},
  author       = {Dihge, Looket and Vallon-Christersson, Johan and Hegardt, Cecilia and Saal, Lao and Häkkinen, Jari and Larsson, Christer and Ehinger, Anna and Loman, Niklas and Malmberg, Martin and Bendahl, Pär-Ola and Borg, Åke and Staaf, Johan and Rydén, Lisa},
  issn         = {1078-0432},
  language     = {eng},
  month        = {07},
  number       = {21},
  pages        = {6368--6381},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical cancer research : an official journal of the American Association for Cancer Research},
  title        = {Prediction of lymph node metastasis in breast cancer by gene expression and clinicopathological models: Development and validation within a population based cohort.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-19-0075},
  doi          = {10.1158/1078-0432.CCR-19-0075},
  volume       = {25},
  year         = {2019},
}