This metadata record describes the data generated and analysed in the study "Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer".The study investigates genetic survival associations in pathogenic variant carriers from Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), genotyped on the OncoArray.Data availability and sourcesA subset of the genotype data that support the findings of this study is publicly available via dbGaP https://identifiers.org/dbgap:phs001321.v1.p1CIMBA 1000 Genomes-imputed genotype data is protected in accordance with the informed consent received from the study participants and therefore cannot be made publicly available. Requests for data can be made to the CIMBA Data Access Coordination Committee. DACC approval is required to access data from the BCFR-ON, EMBRACE, GC-HBOC, HEBCS, HEBON, IHCC, IPOBCS, MCGILL, and OUH studies Phenotype data is stored in a relational database and an output would be a text file. Imputed genotype data can be requested in the QCTOOL dosage format (https://www.well.ox.ac.uk/~gav/qctool_v2/documentation/genotype_file_formats.html), which has been used in these analysesThe contact for data access requests is Lesley McGuffog (ljm26@medschl.cam.ac.uk), Data Manager, Department of Public Health and Primary Care, University of CambridgeNewly discovered survival SNPs were characterized in silico utilizing data from the 1000 genomes and Encode projects as integrated in databases LDlink, RegulomeDB and GeneCards.Candidate genes’ mRNA expression and patient survival was tested in the METABRIC data in European Genome-phenome Archive: EGAD00010000434 (1,302 breast cancer patients).BCAC survival summary results are available from the University of Cambridge BCAC siteAll summary results will be made available on the CIMBA website upon publication of the related article: http://cimba.ccge.medschl.cam.ac.ukThe data that support each table and figure in the related article are summarised in the excel file in this data record.BackgroundThis study investigates the survival of women carrying germline pathogenic BRCA1 or BRCA2 variants. These are the two most important genes linked to breast cancer susceptibility. The great variation in survival rates between tumors with similar characteristics and stage suggests a heritable component, e.g. genetic differences in metastatic potential sensitivity to adjuvant therapy or host factors, like tumor microenvironment interaction, immune surveillance, and efficiency in drug metabolism. Both candidate gene and genome-wide approaches have been employed to find genetic determinants patient prognosis and treatment outcome prediction.Participants women of European ancestry diagnosed with invasive breast cancer before the age of 70 years, enrolled in studies participating in CIMBA. CIMBA studies included in analysis if sufficient follow-up data are available, at least 15 study subjects at risk during the time when five events occurred. Patients were followed from the diagnosis of the first primary breast cancer until death of any causeand censored after 15 years or when lost from follow-upSupplementary table 1 of the related article lists all CIMBA studies, characteristics, sample and cohort sizes. Overall sample sizes: 21 studies for carrier of BRCA1 variants (n = 3,008) 15 studies for carriers of BRCA2 variants (n = 2,009).

Summary

This metadata record provides details of the data supporting the claims of the related manuscript: “Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: A phase II and biomarker study”.

The related study was a single-arm phase II study which investigated the efficacy and safety of cabozantinib combined with nivolumab in metastatic triple-negative breast cancer (mTNBC).

Type of data: whole exome sequencing; linked genotype and phenotype data; genomic profiling; open-label, single-arm, single center phase II study; clinical data

Subject of data: Homo sapiens

Sample size: 18

Population characteristics: Eligible patients had histologically or cytologically confirmed invasive breast cancer with metastatic disease that was measurable per RECIST 1.1 . Tumors were required to be estrogen receptor (ER)-negative and progesterone receptor-negative, defined as < 10% expression by immunohistochemistry, and HER2-negative per the current American Society of Clinical Oncology/College of American Pathologists guidelines

Trial registration number: NCT03316586

Data access

The whole exome and transcriptome data have been deposited in the dbGaP repository under accession https://identifiers.org/dbgap:phs002419.v1.p1. In order to protect patient privacy, these data are controlled access. Details of how to request access can be found on the dbGaP landing page.

The genomic profiling data are in Supplementary Tables 2 and 4.

The supplementary tables of the related article are openly available as part of this figshare data record (as well as via the supplementary materials of the related article) in the file ‘Supplementary Data 1_5-14-21.xlsx’.

Corresponding author(s) for this study

Sara M. Tolaney, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215. Tel: 617-632-3800. Sara_Tolaney@DFCI.HARVARD.EDU

Study approval

The Dana-Farber Cancer Institute institutional review board approved the study and written informed consent from all trial participants was provided before study entry. The study was monitored by the Data Safety Monitoring Board of the Dana-Farber/Harvard Cancer Center.