Digital PCR quantification of ultrahigh ERBB2 copy number identifies poor breast cancer survival after trastuzumab

HER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CEP17 or 2p13.1 as reference, respectively. The accuracy of ddPCR ERBB2 CN was 93.7% and 94.1% in the training and validation groups, respectively. Positive and negative predictive value for the classic HER2 amplification and non-amplifi..., RNA-sequencing data for breast tumors was generated within the SCAN-B initiative.  The processed data file contains ERBB2 original, log2-transformed, and mean adjusted (correcting for 2 group protocols dUTP & TruSeq_*) transcripts per kilobase million (TPM) values as well as all clinical variables used in the analysis.  See README and associated publication for details of SCAN-B RNA-seq data generation and data processing., , # Digital PCR quantification of ultrahigh ERBB2 copy number identifies poor breast cancer survival after trastuzumab: SCAN-B RNA-seq data

[https://doi.org/10.5061/dryad.rv15dv4dm](https://doi.org/10.5061/dryad.rv15dv4dm)

*ABSTRACT*: HER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CE...