The CINSARC signature predicts the clinical outcome in patients with Luminal B breast cancer

CINSARC, a multigene expression signature originally developed in sarcomas, was shown to have prognostic impact in various cancers. We tested the prognostic value for disease-free survival (DFS) of CINSARC in a series of 6035 early-stage invasive primary breast cancers. CINSARC had independent prognostic value in the Luminal B subtype and not in the other subtypes. In Luminal B patients receiving adjuvant endocrine therapy but no chemotherapy, CINSARC identified patients with different 5-year DFS (90% [95%CI 86–95] in low-risk vs. 79% [95%CI 75–84] in high-risk, p = 1.04E−02). Luminal B CINSARC high-risk tumors were predicted to be less sensitive to endocrine therapy and CDK4/6 inhibitors, but more vulnerable to homologous recombination targeting and immunotherapy. We concluded that CINSARC adds prognostic information to that of clinicopathological features in Luminal B breast cancers, which might improve patients’ stratification and better orient adjuvant treatment. Moreover, it identifies potential therapeutic avenues in this aggressive molecular subtype.

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Policy information about availability of computer code Data collection All data collection methods and software used to analyze the data are outlined in the manuscript.

Data analysis
Normalization of public data sets were done by Robust Multi-Array (RMA) with the oligo R package (version 1.46.0) for Affymetrix data and by quantile normalization with the limma R package (version 3.38.3) for other microarray platforms. Supervised analysis was done using a moderated t-test with empirical Bayes statistic included in the limma R package (version 3.38.3). For correction of the multiple-testing hypothesis, False Discovery Rate (FDR) was assessed using qvalue R package (version 2.14. For manuscripts utilizing custom algorithms or software that are central to the research but not yet described in published literature, software must be made available to editors and reviewers. We strongly encourage code deposition in a community repository (e.g. GitHub). See the Nature Research guidelines for submitting code & software for further information.

April 2020
Data Policy information about availability of data All manuscripts must include a data availability statement. This statement should provide the following information, where applicable: -Accession codes, unique identifiers, or web links for publicly available datasets -A list of figures that have associated raw data -A description of any restrictions on data availability The data generated and analysed during this study are described in the following data record: https://doi.org/10.6084/m9.figshare.14350871. All data sets of primary breast cancer were downloaded from the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/), ArrayExpress (https://www.ebi.ac.uk/ arrayexpress/), Genomic Data Commons (GDC, https://portal.gdc.cancer.gov/) and cBioPortal (https://www.cbioportal.org/) databases. All accession IDs are provided in Supplementary Table 10 (Table S10 revised.xlsx), which is included with the data record. The data underlying the figures and tables are contained in the files 'Goncalves_supporting_data.xlsx' and ' Table S8.xlsx', which are included with the data record. A detailed list of the data underlying each figure and table is also available in the file 'Goncalves_2021_underlying_data_list.xlsx', which is included with the data record.

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Sample size
Sample size was determined by availability of gene expression and clinicopathological data at the time of analyses (July 2019). Our series contained 8982 non-redundant invasive breast cancer samples.

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April 2020

Recruitment
Our study is based upon publicly available transcriptomic data of invasive primary breast cancer enrolled in 36 retrospective studies published over a 10-year period between 2002 and 2012. The data collection was done in our laboratory in real time after each publication.

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Our in silico study is based upon public data from published studies in which the informed patients' consent to participate and the ethics and institutional review board were already obtained by authors. The study was approved by our institutional review board (Comité d'Orientation Stratégique, COS).
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