Prognostic value of HER2-low status in breast cancer: a systematic review and meta-analysis

C Molinelli; F Jacobs; E Agostinetto; G Nader-Marta; M Ceppi; M Bruzzone; E Blondeaux; F Schettini; A Prat; G Viale; L Del Mastro; M Lambertini; E de Azambuja

doi:10.1016/j.esmoop.2023.101592

Prognostic value of HER2-low status in breast cancer: a systematic review and meta-analysis

ESMO Open. 2023 Aug;8(4):101592. doi: 10.1016/j.esmoop.2023.101592. Epub 2023 Jul 4.

Authors

C Molinelli¹, F Jacobs², E Agostinetto³, G Nader-Marta⁴, M Ceppi⁵, M Bruzzone⁵, E Blondeaux⁶, F Schettini⁷, A Prat⁸, G Viale⁹, L Del Mastro¹⁰, M Lambertini¹¹, E de Azambuja¹²

Affiliations

¹ Academic Trials Promoting Team, Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genoa. Electronic address: https://twitter.com/ChiaraMolinelli.
² Academic Trials Promoting Team, Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium; Department of Biomedical Sciences, Humanitas University, Milan. Electronic address: https://twitter.com/FlaviaJacobs_.
³ Academic Trials Promoting Team, Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: https://twitter.com/ElisaAgostinett.
⁴ Academic Trials Promoting Team, Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: https://twitter.com/Nader_Guilherme.
⁵ Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
⁶ Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: https://twitter.com/BlondeauxEva.
⁷ Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona; Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona. Electronic address: https://twitter.com/FrancescoSche20.
⁸ Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona; Reveal Genomics, Barcelona, Spain. Electronic address: https://twitter.com/prat_aleix.
⁹ Department of Pathology, IEO European Institute of Oncology IRCCS, Milan.
¹⁰ Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genoa; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: https://twitter.com/delmastro_lucia.
¹¹ Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genoa; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: https://twitter.com/matteolambe.
¹² Academic Trials Promoting Team, Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium; Medical Oncology Department, Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: evandro.deazambuja@hubruxelles.be.

Abstract

Background: Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if HER2-low status has an independent impact on prognosis.

Materials and methods: A systematic literature research was carried out to identify studies comparing survival outcomes of patients affected by HER2-low versus HER2-zero breast cancer. Using random-effects models, pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for progression-free survival (PFS) and overall survival (OS) in the metastatic setting as well as disease-free survival (DFS), OS and pathological complete response (pCR) in the early setting. Subgroup analyses by hormone receptor (HoR) status were carried out. The study protocol is registered on PROSPERO (n.CRD42023390777).

Results: Among 1916 identified records, 42 studies including 1 797 175 patients were eligible. In the early setting, HER2-low status was associated with significant improved DFS (HR 0.86, 95% CI 0.79-0.92, P < 0.001) and OS (HR 0.90, 95% CI 0.85-0.95, P < 0.001) when compared to HER2-zero status. Improved OS was observed for both HoR-positive and HoR-negative HER2-low populations, while DFS improvement was observed only in the HoR-positive subgroup. HER2-low status was significantly associated with a lower rate of pCR as compared to HER2-zero status both in the overall population (OR 0.74, 95% CI 0.62-0.88, P = 0.001) and in the HoR-positive subgroup (OR 0.77, 95% CI 0.65-0.90, P = 0.001). In the metastatic setting, patients with HER2-low breast cancers showed better OS when compared with those with HER2-zero tumours in the overall population (HR 0.94, 95% CI 0.89-0.98, P = 0.008), regardless of HoR status. No significant PFS differences were found.

Conclusions: Compared with HER2-zero status, HER2-low status appears to be associated with a slightly increased OS both in the advanced and early settings, regardless of HoR expression. In the early setting, HER2-low tumours seem to be associated to lower pCR rates, especially if HoR-positive.

Keywords: HER2-low; HER2-zero; breast cancer.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / drug therapy
Disease-Free Survival
Female
Humans
Prognosis
Progression-Free Survival
Proportional Hazards Models