Gampenrieder, SPDezentjé, VLambertini, Mde Nonneville, AMarhold, MLe Du, FCortés Salgado, AAlpuim Costa, DVaz Batista, MChic Ruché, NTinchon, CPetzer, ABlondeaux, EDel Mastro, LTargato, GBertucci, FGonçalves, AViret, FBartsch, RMannsbart, CDeleuze, ARobert, LSaavedra Serrano, CGion Cortés, MSampaio-Alves, MVitorino, MPecen, LSinger, CHarbeck, NRinnerthaler, GGreil, R2022-12-292022-12-292023ESMO Open. 2022 Dec 21;8(1):100747.http://hdl.handle.net/10400.26/42901Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. Patients and methods: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. Results: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). Conclusions: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.engNeoplasias de Mama Triplo NegativasReceptor ErbB-2Receptor, ErbB-2Triple Negative Breast Neoplasmsjournal article10.1016/j.esmoop.2022.100747