PT  - JOURNAL ARTICLE
AU  - Barreca, Marco
AU  - Dugo, Matteo
AU  - Galbardi, Barbara
AU  - Győrffy, Balázs
AU  - ,
AU  - ,
AU  - Valagussa, Pinuccia
AU  - Besozzi, Daniela
AU  - Viale, Giuseppe
AU  - Bianchini, Giampaolo
AU  - Gianni, Luca
AU  - Callari, Maurizio
TI  - Development and validation of a gene expression score to account for tumour purity and improve prognostication in breast cancer
AID  - 10.1101/2024.02.23.581701
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.02.23.581701
4099  - http://biorxiv.org/content/early/2024/02/27/2024.02.23.581701.short
4100  - http://biorxiv.org/content/early/2024/02/27/2024.02.23.581701.full
AB  - The prevalence of malignant cells in clinical specimens, or tumour purity, is affected by both intrinsic biological factors and extrinsic sampling bias. Molecular characterization of large clinical cohorts is typically performed on bulk samples; data analysis and interpretation can be biased by tumour purity variability. Transcription-based strategies to estimate tumour purity have been proposed, but no breast cancer specific method is available yet.We interrogated over 4400 expression profiles from 9 breast cancer datasets to develop and validate a 9-gene Breast Cancer Purity Score (BCPS). BCPS outperformed existing methods for estimating tumour content. Adjusting transcriptomic profiles using the BCPS reduce sampling bias and aid data interpretation. BCPS-estimated tumour purity improved prognostication in luminal breast cancer, correlated with pathologic complete response in on-treatment biopsies from triple-negative breast cancer patients undergoing neoadjuvant treatment and effectively stratified the risk of relapse in HER2+ residual disease post-neoadjuvant treatment.Competing Interest StatementThe authors have declared no competing interest.ANOVAANalysis Of VArianceAUCArea under the ROC curveBCPSBreast Cancer Purity ScoreCBXCore-BiopsyDEFSDistant Event-Free SurvivalEFSEvent-Free SurvivalFDRFalse Discovery RateFFPEFormalin-Fixed, Paraffin-EmbeddedFNAFine-Needle AspirationFPKMFragments Per Kilobase MillionIDCInvasive Ductal CarcinomaILCInvasive Lobular CanceriTILintraepithelial Tumour-Infiltrating LymphocyteOSOverall SurvivalpCRpathological Complete ResponsePDXPatient-derived xenograftROCReceiver Operating CharacteristicsTILstromal Tumour-Infiltrating LymphocyteTMETumour MicroenvironmentVCAVariance Component Analysis