Data from: 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-amplification
groups was 97.2% and 94.8%, respectively. An identified biological
“ultrahigh” ERBB2 ddPCR CN group had significantly worse survival within
patients treated with adjuvant trastuzumab for both recurrence-free
survival (hazard ratio, HR: 3.3; 95% CI 1.1–9.6; p = 0.031, multivariable
Cox regression) and overall survival (HR: 3.6; 95% CI 1.1–12.6;
p = 0.041). For validation using RNA-seq data as a surrogate, in a
population-based SCAN-B cohort (NCT02306096) of 682 consecutive patients
receiving adjuvant trastuzumab, the ultrahigh-ERBB2 mRNA group had
significantly worse survival. Multiplex ddPCR is useful for ERBB2 CN
estimation and ultrahigh ERBB2 may be a predictive factor for decreased
long-term survival after trastuzumab treatment.