Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer

Trastuzumab, the prototype HER2-directed therapy, has markedly improved survival for women with HER2-positive breast cancers. However, only 40–60% of women with HER2-positive breast cancers achieve a complete pathological response to chemotherapy combined with HER2-directed therapy. The current diag...
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Gespeichert in:

Autor*in:	Adam L. Maddox [verfasserIn] Matthew S. Brehove [verfasserIn] Kiarash R. Eliato [verfasserIn] Andras Saftics [verfasserIn] Eugenia Romano [verfasserIn] Michael F. Press [verfasserIn] Joanne Mortimer [verfasserIn] Veronica Jones [verfasserIn] Daniel Schmolze [verfasserIn] Victoria L. Seewaldt [verfasserIn] Tijana Jovanovic-Talisman [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	super-resolution microscopy breast cancer trastuzumab therapy response HER2 clustering

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 14(2022), 11, p 2795
Übergeordnetes Werk:	volume:14 ; year:2022 ; number:11, p 2795

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers14112795

Katalog-ID:	DOAJ042881579

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callnumber-first	R - Medicine
author	Adam L. Maddox
spellingShingle	Adam L. Maddox misc RC254-282 misc super-resolution microscopy misc breast cancer misc trastuzumab misc therapy response misc HER2 misc clustering misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer
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topic_title	RC254-282 Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer super-resolution microscopy breast cancer trastuzumab therapy response HER2 clustering
topic	misc RC254-282 misc super-resolution microscopy misc breast cancer misc trastuzumab misc therapy response misc HER2 misc clustering misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc super-resolution microscopy misc breast cancer misc trastuzumab misc therapy response misc HER2 misc clustering misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc super-resolution microscopy misc breast cancer misc trastuzumab misc therapy response misc HER2 misc clustering misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer
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title_full	Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer
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author_browse	Adam L. Maddox Matthew S. Brehove Kiarash R. Eliato Andras Saftics Eugenia Romano Michael F. Press Joanne Mortimer Veronica Jones Daniel Schmolze Victoria L. Seewaldt Tijana Jovanovic-Talisman
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title_sort	molecular assessment of her2 to identify signatures associated with therapy response in her2-positive breast cancer
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title_auth	Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer
abstract	Trastuzumab, the prototype HER2-directed therapy, has markedly improved survival for women with HER2-positive breast cancers. However, only 40–60% of women with HER2-positive breast cancers achieve a complete pathological response to chemotherapy combined with HER2-directed therapy. The current diagnostic assays have poor positive-predictive accuracy in identifying therapy-responsive breast cancers. Here, we deployed quantitative single molecule localization microscopy to assess the molecular features of HER2 in a therapy-responsive setting. Using fluorescently labeled trastuzumab as a probe, we first compared the molecular features of HER2 in trastuzumab-sensitive (BT-474 and SK-BR-3) and trastuzumab-resistant (BT-474<sup<R</sup< and JIMT-1) cultured cell lines. Trastuzumab-sensitive cells had significantly higher detected HER2 densities and clustering. We then evaluated HER2 in pre-treatment core biopsies from women with breast cancer undergoing neoadjuvant therapy. A complete pathological response was associated with a high detected HER2 density and significant HER2 clustering. These results established the nano-organization of HER2 as a potential signature of therapy-responsive disease.
abstractGer	Trastuzumab, the prototype HER2-directed therapy, has markedly improved survival for women with HER2-positive breast cancers. However, only 40–60% of women with HER2-positive breast cancers achieve a complete pathological response to chemotherapy combined with HER2-directed therapy. The current diagnostic assays have poor positive-predictive accuracy in identifying therapy-responsive breast cancers. Here, we deployed quantitative single molecule localization microscopy to assess the molecular features of HER2 in a therapy-responsive setting. Using fluorescently labeled trastuzumab as a probe, we first compared the molecular features of HER2 in trastuzumab-sensitive (BT-474 and SK-BR-3) and trastuzumab-resistant (BT-474<sup<R</sup< and JIMT-1) cultured cell lines. Trastuzumab-sensitive cells had significantly higher detected HER2 densities and clustering. We then evaluated HER2 in pre-treatment core biopsies from women with breast cancer undergoing neoadjuvant therapy. A complete pathological response was associated with a high detected HER2 density and significant HER2 clustering. These results established the nano-organization of HER2 as a potential signature of therapy-responsive disease.
abstract_unstemmed	Trastuzumab, the prototype HER2-directed therapy, has markedly improved survival for women with HER2-positive breast cancers. However, only 40–60% of women with HER2-positive breast cancers achieve a complete pathological response to chemotherapy combined with HER2-directed therapy. The current diagnostic assays have poor positive-predictive accuracy in identifying therapy-responsive breast cancers. Here, we deployed quantitative single molecule localization microscopy to assess the molecular features of HER2 in a therapy-responsive setting. Using fluorescently labeled trastuzumab as a probe, we first compared the molecular features of HER2 in trastuzumab-sensitive (BT-474 and SK-BR-3) and trastuzumab-resistant (BT-474<sup<R</sup< and JIMT-1) cultured cell lines. Trastuzumab-sensitive cells had significantly higher detected HER2 densities and clustering. We then evaluated HER2 in pre-treatment core biopsies from women with breast cancer undergoing neoadjuvant therapy. A complete pathological response was associated with a high detected HER2 density and significant HER2 clustering. These results established the nano-organization of HER2 as a potential signature of therapy-responsive disease.
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title_short	Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer
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up_date	2024-07-03T14:32:02.036Z
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Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer

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