Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study

Abstract Purpose The antibody–drug conjugate trastuzumab deruxtecan has proven to be not only efficient in patients with HER2+ breast cancers (BC), but also in those patients with so-called HER2-low BC. HER2-low tumors are well described in the general BC population, but not in patients with invasiv...

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Main Authors: Karen Van Baelen, Ha-Linh Nguyen, François Richard, Gitte Zels, Maria Margarete Karsten, Guilherme Nader-Marta, Peter Vermeulen, Luc Dirix, Adam David Dordevic, Evandro de Azambuja, Denis Larsimont, Marion Maetens, Elia Biganzoli, Hans Wildiers, Ann Smeets, Ines Nevelsteen, Patrick Neven, Giuseppe Floris, Christine Desmedt
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Language:English
Published: BMC 2025-06-01
Series:Breast Cancer Research
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Online Access:https://doi.org/10.1186/s13058-025-02058-x
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author Karen Van Baelen
Ha-Linh Nguyen
François Richard
Gitte Zels
Maria Margarete Karsten
Guilherme Nader-Marta
Peter Vermeulen
Luc Dirix
Adam David Dordevic
Evandro de Azambuja
Denis Larsimont
Marion Maetens
Elia Biganzoli
Hans Wildiers
Ann Smeets
Ines Nevelsteen
Patrick Neven
Giuseppe Floris
Christine Desmedt
author_facet Karen Van Baelen
Ha-Linh Nguyen
François Richard
Gitte Zels
Maria Margarete Karsten
Guilherme Nader-Marta
Peter Vermeulen
Luc Dirix
Adam David Dordevic
Evandro de Azambuja
Denis Larsimont
Marion Maetens
Elia Biganzoli
Hans Wildiers
Ann Smeets
Ines Nevelsteen
Patrick Neven
Giuseppe Floris
Christine Desmedt
author_sort Karen Van Baelen
collection DOAJ
description Abstract Purpose The antibody–drug conjugate trastuzumab deruxtecan has proven to be not only efficient in patients with HER2+ breast cancers (BC), but also in those patients with so-called HER2-low BC. HER2-low tumors are well described in the general BC population, but not in patients with invasive lobular carcinoma (ILC). Here, we aimed at analyzing the association of HER2-low with clinicopathological features and survival outcomes in patients with early-stage pure ILC. Methods A multicentric retrospective cohort of patients diagnosed with stage I-III estrogen receptor positive (ER+) HER2 negative (HER2-) ILC between 01/01/2000 and 12/31/2020 was assembled. HER2- disease was categorized further by immunohistochemical (IHC) score into HER2 0, HER2 1+ and HER2 2+ following time appropriate ASCO/CAP guidelines from 2007 onward and by local guidelines prior to 2007. The association of HER2-low (HER2 1+ and 2+) with clinicopathological variables was assessed using multinomial logistic regression. Survival analyses were performed to evaluate the association of HER2-low with disease-free (DFS), distant recurrence-free (DRFS) and overall survival (OS). Results The data of 2098 patients with ER+ HER2- ILC was collected of which 1103 (52.6%) had a HER2-low tumor. Of these 716 (34.1%) had an IHC score of HER2 1+ and 387 (18.4%) of HER2 2+. In multivariable analysis, both tumor size of ≥ 2cm (OR: 1.37; 95%CI 1.01 – 1.87; p-value 0.042) and multifocality (OR: 1.55; 95%CI 1.11 – 2.15; p-value 0.009) were associated with HER2-low. HER2-low was associated with worse DFS (HR: 1.32; 95%CI 1.06 − 1.66; p-value 0.015) and OS (HR: 1.42; 95%CI 1.12 − 1.81; p-value 0.004) as compared to HER2 0. No association of HER2-low with DRFS was observed. Conclusions HER2-low is present in more than half of the patients with early ER+ HER2- pure ILCs and is associated with larger tumor size and multifocality. HER2-low is associated with a worse DFS and OS as compared to HER2 0.
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spelling doaj-art-52831d5e7c6d49c8aa5614bade242be72025-08-20T02:39:44ZengBMCBreast Cancer Research1465-542X2025-06-0127111310.1186/s13058-025-02058-xAssociation of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric studyKaren Van Baelen0Ha-Linh Nguyen1François Richard2Gitte Zels3Maria Margarete Karsten4Guilherme Nader-Marta5Peter Vermeulen6Luc Dirix7Adam David Dordevic8Evandro de Azambuja9Denis Larsimont10Marion Maetens11Elia Biganzoli12Hans Wildiers13Ann Smeets14Ines Nevelsteen15Patrick Neven16Giuseppe Floris17Christine Desmedt18Department of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU LeuvenDepartment of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU LeuvenDepartment of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU LeuvenDepartment of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU LeuvenDepartment of Gynecology and Breast Center, Charité Universitätsmedizin BerlinInstitut Jules Bordet, l’Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B)Department of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU LeuvenTranslational Cancer Research Unit, Oncology Centre AntwerpDepartment of Gynecology and Breast Center, Charité Universitätsmedizin BerlinInstitut Jules Bordet, l’Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B)Institut Jules Bordet, l’Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B)Department of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU LeuvenDepartment of Clinical Sciences and Community Health & DSRC, Unit of Medical Statistics, Biometry and Epidemiology “Giulio A. Maccacaro”, University of MilanDepartment of General Medical Oncology, University Hospitals LeuvenDepartment of Surgical Oncology, University Hospitals LeuvenDepartment of Surgical Oncology, University Hospitals LeuvenDepartment of Gynecological Oncology, University Hospitals LeuvenDepartment of Pathology, University Hospitals LeuvenDepartment of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU LeuvenAbstract Purpose The antibody–drug conjugate trastuzumab deruxtecan has proven to be not only efficient in patients with HER2+ breast cancers (BC), but also in those patients with so-called HER2-low BC. HER2-low tumors are well described in the general BC population, but not in patients with invasive lobular carcinoma (ILC). Here, we aimed at analyzing the association of HER2-low with clinicopathological features and survival outcomes in patients with early-stage pure ILC. Methods A multicentric retrospective cohort of patients diagnosed with stage I-III estrogen receptor positive (ER+) HER2 negative (HER2-) ILC between 01/01/2000 and 12/31/2020 was assembled. HER2- disease was categorized further by immunohistochemical (IHC) score into HER2 0, HER2 1+ and HER2 2+ following time appropriate ASCO/CAP guidelines from 2007 onward and by local guidelines prior to 2007. The association of HER2-low (HER2 1+ and 2+) with clinicopathological variables was assessed using multinomial logistic regression. Survival analyses were performed to evaluate the association of HER2-low with disease-free (DFS), distant recurrence-free (DRFS) and overall survival (OS). Results The data of 2098 patients with ER+ HER2- ILC was collected of which 1103 (52.6%) had a HER2-low tumor. Of these 716 (34.1%) had an IHC score of HER2 1+ and 387 (18.4%) of HER2 2+. In multivariable analysis, both tumor size of ≥ 2cm (OR: 1.37; 95%CI 1.01 – 1.87; p-value 0.042) and multifocality (OR: 1.55; 95%CI 1.11 – 2.15; p-value 0.009) were associated with HER2-low. HER2-low was associated with worse DFS (HR: 1.32; 95%CI 1.06 − 1.66; p-value 0.015) and OS (HR: 1.42; 95%CI 1.12 − 1.81; p-value 0.004) as compared to HER2 0. No association of HER2-low with DRFS was observed. Conclusions HER2-low is present in more than half of the patients with early ER+ HER2- pure ILCs and is associated with larger tumor size and multifocality. HER2-low is associated with a worse DFS and OS as compared to HER2 0.https://doi.org/10.1186/s13058-025-02058-xInvasive lobular carcinomaHER2-lowClinicopathological featuresSurvival
spellingShingle Karen Van Baelen
Ha-Linh Nguyen
François Richard
Gitte Zels
Maria Margarete Karsten
Guilherme Nader-Marta
Peter Vermeulen
Luc Dirix
Adam David Dordevic
Evandro de Azambuja
Denis Larsimont
Marion Maetens
Elia Biganzoli
Hans Wildiers
Ann Smeets
Ines Nevelsteen
Patrick Neven
Giuseppe Floris
Christine Desmedt
Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study
Breast Cancer Research
Invasive lobular carcinoma
HER2-low
Clinicopathological features
Survival
title Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study
title_full Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study
title_fullStr Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study
title_full_unstemmed Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study
title_short Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study
title_sort association of her2 low with clinicopathological features in patients with early invasive lobular breast cancer an international multicentric study
topic Invasive lobular carcinoma
HER2-low
Clinicopathological features
Survival
url https://doi.org/10.1186/s13058-025-02058-x
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