Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry.

HER2-low HER2-negative HER2-positive Metastatic breast cancer OS PFS Real-world data Registry

Journal

Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353

Informations de publication

Date de publication:
14 12 2021
Historique:
received: 20 07 2021
accepted: 28 11 2021
entrez: 15 12 2021
pubmed: 16 12 2021
medline: 17 3 2022
Statut: epublish

Résumé

About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

Sections du résumé

BACKGROUND
About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC).
PATIENTS AND METHODS
The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included.
RESULTS
As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients.
CONCLUSION
Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

Identifiants

pubmed: 34906198
doi: 10.1186/s13058-021-01492-x
pii: 10.1186/s13058-021-01492-x
pmc: PMC8670265
doi:

Substances chimiques

Receptor, ErbB-2 EC 2.7.10.1

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112

Informations de copyright

© 2021. The Author(s).

Références

Nat Commun. 2018 Mar 23;9(1):1219
pubmed: 29572535
Clin Cancer Res. 2016 Oct 15;22(20):5097-5108
pubmed: 27026201
Ann Oncol. 2008 Oct;19(10):1706-12
pubmed: 18544559
J Clin Oncol. 2020 Feb 10;38(5):444-453
pubmed: 31821109
J Clin Oncol. 2020 Jun 10;38(17):1887-1896
pubmed: 32058843
Clin Cancer Res. 2019 Mar 15;25(6):1970-1979
pubmed: 30559169
Surg Today. 2016 Jul;46(7):821-6
pubmed: 26467559
Endocr Relat Cancer. 2015 Oct;22(5):725-33
pubmed: 26187126
Am J Surg Pathol. 2009 May;33(5):759-67
pubmed: 19252432
Breast Cancer Res Treat. 2020 Feb;179(3):687-697
pubmed: 31811505
Br J Cancer. 2017 Dec 5;117(12):1736-1742
pubmed: 29065110
Nat Rev Drug Discov. 2017 May;16(5):315-337
pubmed: 28303026
Mod Pathol. 2001 Nov;14(11):1079-86
pubmed: 11706067
Lancet Oncol. 2019 Aug;20(8):1124-1135
pubmed: 31257177
J Clin Oncol. 2018 Jul 10;36(20):2105-2122
pubmed: 29846122
Clin Cancer Res. 2017 Jun 1;23(11):2702-2712
pubmed: 28151718
Eur J Cancer. 2021 Sep;155:1-12
pubmed: 34311211
Cancer Res. 2003 Apr 1;63(7):1445-8
pubmed: 12670887
J Clin Oncol. 2020 Jun 10;38(17):1951-1962
pubmed: 32330069
NPJ Breast Cancer. 2021 Jan 4;7(1):1
pubmed: 33397968
Arch Pathol Lab Med. 2014 Feb;138(2):213-9
pubmed: 24164555
Oncologist. 2012;17(11):1418-25
pubmed: 22951668
J Clin Invest. 2020 Aug 3;130(8):4252-4265
pubmed: 32657779
Clin Cancer Res. 2001 Jun;7(6):1669-75
pubmed: 11410505
BMC Cancer. 2018 Mar 27;18(1):348
pubmed: 29587674

Auteurs

Simon Peter Gampenrieder (SP)

Department of Internal Medicine III With Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020, Salzburg, Austria.
Laboratory for Immunological and Molecular Cancer Research (LIMCR) and Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg Cancer Research Institute (SCRI), Salzburg, Austria.
Cancer Cluster Salzburg, Salzburg, Austria.

Gabriel Rinnerthaler (G)

Department of Internal Medicine III With Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020, Salzburg, Austria.
Laboratory for Immunological and Molecular Cancer Research (LIMCR) and Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg Cancer Research Institute (SCRI), Salzburg, Austria.
Cancer Cluster Salzburg, Salzburg, Austria.

Christoph Tinchon (C)

Internal Medicine - Department for Haemato-Oncology, LKH Hochsteiermark-Leoben, Leoben, Austria.

Andreas Petzer (A)

Internal Medicine I for Hematology With Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz Barmherzige Schwestern - Elisabethinen, Linz, Austria.

Marija Balic (M)

Division of Oncology, Department for Internal Medicine, Medical University Graz, Graz, Austria.

Sonja Heibl (S)

Department of Internal Medicine IV, Klinikum Wels-Grieskirchen GmbH, Wels, Austria.

Clemens Schmitt (C)

Department of Hematology and Internal Oncology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.

August Felix Zabernigg (AF)

Department of Internal Medicine, County Hospital Kufstein, Kufstein, Austria.

Daniel Egle (D)

Department of Gynaecology, Medical University Innsbruck, Innsbruck, Austria.

Margit Sandholzer (M)

Department of Internal Medicine II, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.

Christian Fridolin Singer (CF)

Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Florian Roitner (F)

Department of Internal Medicine II, Hospital Braunau, Braunau, Austria.

Christopher Hager (C)

Breast Center Dornbirn, Dornbirn, Austria.

Johannes Andel (J)

Department of Internal Medicine II, Pyrn-Eisenwurzen Klinikum Steyr, Steyr, Austria.

Michael Hubalek (M)

Department of Gynecology, Breast Health Center Schwaz, Schwaz, Austria.

Michael Knauer (M)

Breast Center Eastern Switzerland, St. Gallen, Switzerland.

Richard Greil (R)

Department of Internal Medicine III With Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020, Salzburg, Austria. r.greil@salk.at.
Laboratory for Immunological and Molecular Cancer Research (LIMCR) and Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg Cancer Research Institute (SCRI), Salzburg, Austria. r.greil@salk.at.
Cancer Cluster Salzburg, Salzburg, Austria. r.greil@salk.at.

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