Abstract PD3-09: Efficacy of HER2 inhibitors in metastatic breast cancer by discordance in HER2 amplification status between primary and metastatic breast cancer
Authors: E Van Raemdonck, P Berteloot, A Laenen, S Han, E Van Nieuwenhuysen, R Salihi, N Concin, I Vergote, G Floris, H Wildiers, K Punie, P Neven
Journal: Cancer Research (2019)

Abstract Purpose: In stage IV breast cancer (BC), discordance in the human epidermal growth factor receptor 2 (HER2) amplification status between primary and metastatic BC might affect efficacy of HER2-targeted agents. We studied progression free (PFS) and overall survival (OS) dependent on HER2 concordance in patients treated with a first line taxane-trastuzumab combination and later line trastuzumab-emtansine (T-DM1). Patients and Methods: This retrospective monocentric study included 76 patients with metastatic BC under treatment with trastuzumab in which a biopsy from both the primary and metastatic site was available. HER2 amplification status, sex-steroid receptor status, Nottingham prognostic index, distant metastasis-free interval and consecutive lines of therapy were retrieved from patients' reports. The Kaplan-Meier method was used for estimating PFS/OS and log-rank test for analyzing between group differences. A Cox model is used for testing difference between groups while correcting for Pertuzumab. Multivariable Cox regression is used to model OS as a function group, correcting for possible confounders. Results: Discordance in HER2 amplification status was seen in 30 out of 76 patients (39%), 11 patients lost HER2 amplification in the metastatic lesion (HER2lost) while 19 acquired HER2 amplification (HER2acquired). The other 46 patients had a HER2 amplification on both primary and metastatic site (HER2stable). The HER2lost group had a significant lower median PFS (PFS= 5.5 months) for taxane-trastuzumab, after correcting for pertuzumab, compared to the HER2stable group (PFS= 9 months, corrected p= 0.0146) and HER2acquired group (PFS=14 months, corrected p=0.0121). For T-DM1 treatment, both discordant groups, HER2acquired (PFS=1.1 months, p=0.0373) and HER2lost (PFS=1.5 months, p=0.0116), had a significant lower PFS compared to the HER2stable group (PFS=6.0 months). After correcting for possible confounders, HER2lost had a significant worse OS compared to HER2stable (HR 0.187, 95% CI 0.079 – 0.439) and HER2acquired (HR 0.147, 95% 0.058-0.378). Conclusion: Loss of HER2 amplification in metastatic lesions seems to have a negative predictive value for PFS on HER2-targeted agents and negative prognostic impact on OS. Acquiring of HER2 amplification was predictive for lower PFS on T-DM1 but wasn't predictive for lower PFS on taxane-trastuzumab. Citation Format: Van Raemdonck E, Berteloot P, Laenen A, Han S, Van Nieuwenhuysen E, Salihi R, Concin N, Vergote I, Floris G, Wildiers H, Punie K, Neven P. Efficacy of HER2 inhibitors in metastatic breast cancer by discordance in HER2 amplification status between primary and metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-09.