Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group
Simon Peter Gampenrieder, Vincent O. Dezentjé, Matteo Lambertini, Alexandre de Nonneville, Maximilian Marhold, Fanny Le Du, Alfonso Cortés Salgado, Diogo Alpuim Costa, Marta Vaz Batista, N. Chic Ruché, Christoph Tinchon, Andreas Petzer, Eva Blondeaux, Lucia Del Mastro, Giada Targato, François Bertucci, Anthony Gonçalvès, F. Viret, Rupert Bartsch, C. Mannsbart, Antoine Deleuze, L. Robert, Cristina Saavedra, Mar Cortes, Mafalda Sampaio-Alves, M. Vitorino, Ladislav Pecen, Christian F. Singer, Nadia Harbeck, Gabriel Rinnerthaler, Richard Greil, Marija Balić, Sonja Heibl, August Zabernigg, Daniel Egle, Margit Sandholzer, Florian Roitner, Johannes Andel, Petra Pichler, Christopher Hager, Michael Knauer, Michael Hubalek, Claudia Bighin, Michelino De Laurentiis, Sabino De Placido, Fabio Puglisi, Luca Boni, Amelie de Gregorio, Tom Degenhardt, Luigi Formisano, Karin Beelen, Timothy Robinson, Amanda Fitzpatrick, Véronique Dièras, Volkmar Müller, Alessandra Gennari, Sabine Linn, Sofía Braga, Javier Cortés, Carlo Palmieri
Abstract
•This was an international, multicenter analysis including 691 patients with metastatic TNBC.•The frequency of HER2-low was 32.0% (95% CI 28.5% to 35.5%).•Similar frequencies were seen in metastases (29.8%) and primary tumors (33.4%; P = 0.324).•There was no statistically different OS between HER2-low and HER2-0 TNBC (HR 1.00; P = 0.969).•There was no significant impact of HER2-low on OS in multivariable analysis (HR 0.95; P = 0.545). BackgroundTriple-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 methodsWe 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.ResultsIn 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).ConclusionsIn 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. 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. 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. 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). 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.