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Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2 + breast carcinoma

Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2 + breast carcinoma
Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2 + breast carcinoma
Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer the presence of CLS has been correlated to high body mass index (BMI), larger mammary adipocyte size and postmenopausal status. However, the prognostic significance of CLS in HER2 + breast cancer is still unknown. We investigated the prognostic significance of CLS in a cohort of 69 trastuzumab-naïve and 117 adjuvant trastuzumab-treated patients with primary HER2 + breast cancer. Immunohistochemistry of tumour blocks was performed for CLS and correlated to clinical outcomes. CLS were more commonly found at the adipose-tumour border (B-CLS) (64.8% of patients). The presence of multiple B-CLS was associated with reduced time to metastatic disease (TMD) in trastuzumab treated patients with BMI ≥ 25 kg/m 2 but not those with BMI < 25 kg/m 2. Phenotypic analysis showed the presence of CD32B + B-CLS was strongly correlated to BMI ≥ 25 kg/m 2 and reduced TMD in trastuzumab treated patients. Multivariable analysis suggested that CD32B + B-CLS positive tumours are associated with shorter TMD in trastuzumab-treated patients (HR 4.2 [95%CI, (1.01-17.4). This study indicates adipose-tumour border crown-like structures that are CD32B + potentially represent a biomarker for improved personalisation of treatment in HER2-overexpressed breast cancer patients.
Adipose Tissue/metabolism, Breast Neoplasms/pathology, Breast/pathology, Female, Humans, Prognosis, Receptor, ErbB-2/metabolism, Trastuzumab/metabolism
2045-2322
Birts, Charles N.
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Savva, Constantinos
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Laversin, Stéphanie A.
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Lefas, Alicia
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Krishnan, Jamie
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Schapira, Aron
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Ashton-Key, Margaret
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Crispin, Max
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Johnson, Peter W.M.
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Blaydes, Jeremy P.
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Copson, Ellen
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Cutress, Ramsey I.
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Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Birts, Charles N.
8689ddad-ba47-4ca6-82c5-001315dbd250
Savva, Constantinos
d6e87674-1443-41f4-84ba-81c1ccfeb3d7
Laversin, Stéphanie A.
e9122da5-bfb0-4260-b7db-659fb855e898
Lefas, Alicia
393ac725-8218-423c-a63a-d5ee7db50842
Krishnan, Jamie
d468aa8a-78ad-44ad-8030-609c5d646e97
Schapira, Aron
b7c189ea-55c2-43ca-8818-cf68b09b8740
Ashton-Key, Margaret
5994ca63-021e-44b1-86c4-b7ae53321101
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Johnson, Peter W.M.
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Blaydes, Jeremy P.
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Copson, Ellen
a94cdbd6-f6e2-429d-a7c0-462c7da0e92b
Cutress, Ramsey I.
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Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2

Birts, Charles N., Savva, Constantinos, Laversin, Stéphanie A., Lefas, Alicia, Krishnan, Jamie, Schapira, Aron, Ashton-Key, Margaret, Crispin, Max, Johnson, Peter W.M., Blaydes, Jeremy P., Copson, Ellen, Cutress, Ramsey I. and Beers, Stephen A. (2022) Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2 + breast carcinoma. Scientific Reports, 12 (1), [7802]. (doi:10.1038/s41598-022-11696-6).

Record type: Article

Abstract

Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer the presence of CLS has been correlated to high body mass index (BMI), larger mammary adipocyte size and postmenopausal status. However, the prognostic significance of CLS in HER2 + breast cancer is still unknown. We investigated the prognostic significance of CLS in a cohort of 69 trastuzumab-naïve and 117 adjuvant trastuzumab-treated patients with primary HER2 + breast cancer. Immunohistochemistry of tumour blocks was performed for CLS and correlated to clinical outcomes. CLS were more commonly found at the adipose-tumour border (B-CLS) (64.8% of patients). The presence of multiple B-CLS was associated with reduced time to metastatic disease (TMD) in trastuzumab treated patients with BMI ≥ 25 kg/m 2 but not those with BMI < 25 kg/m 2. Phenotypic analysis showed the presence of CD32B + B-CLS was strongly correlated to BMI ≥ 25 kg/m 2 and reduced TMD in trastuzumab treated patients. Multivariable analysis suggested that CD32B + B-CLS positive tumours are associated with shorter TMD in trastuzumab-treated patients (HR 4.2 [95%CI, (1.01-17.4). This study indicates adipose-tumour border crown-like structures that are CD32B + potentially represent a biomarker for improved personalisation of treatment in HER2-overexpressed breast cancer patients.

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Accepted/In Press date: 20 April 2022
Published date: 24 May 2022
Additional Information: Funding Information: CNB is supported by the Against Breast Cancer Lectureship. CS and SAB receive funding from Cancer Research UK. RIC has received research funding from Breast Cancer Now (BCN) and World Cancer Research Fund (WCRF) UK, as part of the WCRF International grant programme. EC has received research funding from BCN and WCRF UK, as part of the WCRF International grant programme. CNB, SAB and MC gratefully acknowledge a programme grant from Against Breast Cancer ( www.againstbreastcancer.org.uk ; UK Charity 1121258). Funding Information: SAB has acted as a consultant for a number of biotech companies and has received institutional support for grants and patents from BioInvent International. Medical body composition analysers provided by SECA as part of an investigator-led Collaborative Research Agreement between Seca GmbH & Co. KG. (Hamburg, Germany), University Hospital Southampton NHS Foundation Trust and the University of Southampton have been utilised by RIC for research purposes. EC has received: honorarium from Astra-Zeneca, Novartis, Pfizer, Roche, Lilly; Advisory boards: Pfizer, Nanostring, Lilly; Expert panel participation: World Cancer Research Fund. RIC and EC report Research funding from SECA and Astra-Zeneca. CNB, CS, SAL, AL, JK, AS, MA, MC, PWMJ, JPB declare no competing interests. Publisher Copyright: © 2022, The Author(s).
Keywords: Adipose Tissue/metabolism, Breast Neoplasms/pathology, Breast/pathology, Female, Humans, Prognosis, Receptor, ErbB-2/metabolism, Trastuzumab/metabolism

Identifiers

Local EPrints ID: 458130
URI: http://eprints.soton.ac.uk/id/eprint/458130
ISSN: 2045-2322
PURE UUID: 4638e47a-7981-4a32-a6c3-20b6b3ee5ebc
ORCID for Charles N. Birts: ORCID iD orcid.org/0000-0002-0368-8766
ORCID for Constantinos Savva: ORCID iD orcid.org/0000-0003-0805-4719
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694
ORCID for Jeremy P. Blaydes: ORCID iD orcid.org/0000-0001-8525-0209
ORCID for Stephen A. Beers: ORCID iD orcid.org/0000-0002-3765-3342

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Date deposited: 28 Jun 2022 17:37
Last modified: 29 Oct 2022 01:58

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Contributors

Author: Stéphanie A. Laversin
Author: Alicia Lefas
Author: Jamie Krishnan
Author: Aron Schapira
Author: Margaret Ashton-Key
Author: Max Crispin ORCID iD
Author: Peter W.M. Johnson
Author: Ellen Copson

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