Identification, clinical-pathological characteristics and treatment outcomes of patients with metastatic breast cancer and somatic human epidermal growth factor receptor 2 (ERBB2) mutations

PurposeThe human epidermal growth factor receptor 2 (ERBB2) may harbour somatic mutations that drive breast tumorigenesis. Here, we study prevalence, tumour characteristics and disease outcome of ERBB2 mutations in a large unselected cohort of metastatic breast cancer (mBC) patients.MethodsWe retrospectively included all mBC patients with sufficient primary breast tumour, diagnosed between 2000 and 2015 (n=775). Genomic DNA was subjected to a targeted-resequencing assay to identify hotspot mutations in exon 8, 17, 19, 20, and 21 of ERBB2. We studied demographics, tumour characteristics, median distant disease-free survival (DDFS), using a time-to-event analysis and time to progression (TTP) and overall survival (OS) upon metastasis, using Kaplan-Meier and log-rank statistics to assess differences between ERBB2-mutation statuses.ResultsERBB2 mutations were observed in 1.8% of the samples (13/721). Patient and tumour characteristics were independent of ERBB2 mutations. Luminal ERBB2-mutated (ERBB2(mut+)) cases (n=5) had a shorter DDFS than ERBB2(mut-) cases (median DDFS 0.8 vs.>4.0years, p=0.02). ER-positive ERBB2(mut+) patients who received an aromatase inhibitor (AI) as first-line treatment (stage IV disease) had a worse TTP vs. ERBB2(mut-) patients (n=3 vs. 156; median TTP 103 vs. 311days, p=0.04). OS for all subtypes was lower for ERBB2(mut+) vs. ERBB2(mut-) cases (n=11 vs. 669; median OS 1.1 vs. 2.3years, p=0.46).ConclusionERBB2(mut+) are rare in patients in whom mBC developed and no evidence was found for an association with specific types of BC or patient characteristics, although outcomes of ERBB2(mut+) carriers might be worse. The latter, however, needs to be validated in larger populations.