Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group

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 abou...

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Published in:	ESMO open Vol. 8; no. 1; p. 100747
Main Authors:	Gampenrieder, S.P., Dezentjé, V., Lambertini, M., de Nonneville, A., Marhold, M., Le Du, F., Cortés Salgado, A., Alpuim Costa, D., Vaz Batista, M., Chic Ruché, N., Tinchon, C., Petzer, A., Blondeaux, E., Del Mastro, L., Targato, G., Bertucci, F., Gonçalves, A., Viret, F., Bartsch, R., Mannsbart, C., Deleuze, A., Robert, L., Saavedra Serrano, C., Gion Cortés, M., Sampaio-Alves, M., Vitorino, M., Pecen, L., Singer, C., Harbeck, N., Rinnerthaler, G., Greil, R., Balic, Marija, Heibl, Sonja, Zabernigg, August Felix, Egle, Daniel, Sandholzer, Margit, Roitner, Florian, Andel, Johannes, Pichler, Petra, Hager, Christopher, Knauer, Michael, Hubalek, Michael, Bighin, Claudia, De Laurentiis, Michelino, De Placido, Sabino, Puglisi, Fabio, Boni, Luca, de Gregorio, Amelie, Degenhardt, Tom, Formisano, Luigi, Beelen, Karin, Robinson, Timothy, Fitzpatrick, Amanda, Dieras, Veronique, Muller, Volkmar, Gennari, Alessandra, Linn, Sabine, Braga, Sofia, Cortes, Javier, Palmieri, Carlo
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-02-2023 Elsevier
Subjects:	Europe HER2-low Humans metastatic Original Research Prognosis real-world data Retrospective Studies Triple Negative Breast Neoplasms - drug therapy Triple Negative Breast Neoplasms - metabolism triple-negative breast cancer Europe triple-negative breast cancer HER2-low real-world data metastatic OS prognosis
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Summary:	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. •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).
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Contributed equally to this work.
ISSN:	2059-7029 2059-7029
DOI:	10.1016/j.esmoop.2022.100747