Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis

Purpose Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer pati...

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Veröffentlicht in:Breast cancer research and treatment 2018-05, Vol.169 (1), p.83-92
Hauptverfasser: García Garre, Elisa, Luengo Gil, Ginés, Montoro García, Silvia, Gonzalez Billalabeitia, Enrique, Zafra Poves, Marta, García Martinez, Elena, Roldán Schilling, Vanessa, Navarro Manzano, Esther, Ivars Rubio, Alejandra, Lip, Gregory Y. H., Ayala de la Peña, Francisco
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container_end_page 92
container_issue 1
container_start_page 83
container_title Breast cancer research and treatment
container_volume 169
creator García Garre, Elisa
Luengo Gil, Ginés
Montoro García, Silvia
Gonzalez Billalabeitia, Enrique
Zafra Poves, Marta
García Martinez, Elena
Roldán Schilling, Vanessa
Navarro Manzano, Esther
Ivars Rubio, Alejandra
Lip, Gregory Y. H.
Ayala de la Peña, Francisco
description Purpose Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer. Methods We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1–0.5 μm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA. Results Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy ( P  = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response ( P  = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04–0.87; P  = 0.02) and progression free survival (HR 0.30; 95% CI 0.09–0.99; P  = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis. Conclusions Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.
doi_str_mv 10.1007/s10549-017-4656-z
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H. ; Ayala de la Peña, Francisco</creator><creatorcontrib>García Garre, Elisa ; Luengo Gil, Ginés ; Montoro García, Silvia ; Gonzalez Billalabeitia, Enrique ; Zafra Poves, Marta ; García Martinez, Elena ; Roldán Schilling, Vanessa ; Navarro Manzano, Esther ; Ivars Rubio, Alejandra ; Lip, Gregory Y. H. ; Ayala de la Peña, Francisco</creatorcontrib><description>Purpose Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer. Methods We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1–0.5 μm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA. Results Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy ( P  = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response ( P  = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04–0.87; P  = 0.02) and progression free survival (HR 0.30; 95% CI 0.09–0.99; P  = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis. Conclusions Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-017-4656-z</identifier><identifier>PMID: 29340882</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adjuvant chemotherapy ; Adult ; Aged ; Angiogenesis ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Breast cancer ; Breast Neoplasms - blood ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cancer metastasis ; Cancer patients ; Cancer research ; Care and treatment ; Cell-Derived Microparticles - genetics ; Cell-Derived Microparticles - pathology ; Chemotherapy ; Clinical outcomes ; Clinical Trial ; Development and progression ; Disease-Free Survival ; Endothelium ; Endothelium - pathology ; Enzyme-linked immunosorbent assay ; Female ; Humans ; Medical prognosis ; Medicine ; Medicine &amp; Public Health ; Metastases ; Metastasis ; Microparticles ; Middle Aged ; Neoadjuvant Therapy ; Oncology ; Patient outcomes ; Prognosis ; Survival ; Treatment Outcome ; Vascular endothelial growth factor</subject><ispartof>Breast cancer research and treatment, 2018-05, Vol.169 (1), p.83-92</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Springer</rights><rights>Breast Cancer Research and Treatment is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-52205aed7f5c03fd46e8e48823edf7aae9c908ff89b40a91d942785a6b15dfed3</citedby><cites>FETCH-LOGICAL-c536t-52205aed7f5c03fd46e8e48823edf7aae9c908ff89b40a91d942785a6b15dfed3</cites><orcidid>0000-0001-6311-920X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-017-4656-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-017-4656-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29340882$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>García Garre, Elisa</creatorcontrib><creatorcontrib>Luengo Gil, Ginés</creatorcontrib><creatorcontrib>Montoro García, Silvia</creatorcontrib><creatorcontrib>Gonzalez Billalabeitia, Enrique</creatorcontrib><creatorcontrib>Zafra Poves, Marta</creatorcontrib><creatorcontrib>García Martinez, Elena</creatorcontrib><creatorcontrib>Roldán Schilling, Vanessa</creatorcontrib><creatorcontrib>Navarro Manzano, Esther</creatorcontrib><creatorcontrib>Ivars Rubio, Alejandra</creatorcontrib><creatorcontrib>Lip, Gregory Y. H.</creatorcontrib><creatorcontrib>Ayala de la Peña, Francisco</creatorcontrib><title>Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer. Methods We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1–0.5 μm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA. Results Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy ( P  = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response ( P  = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04–0.87; P  = 0.02) and progression free survival (HR 0.30; 95% CI 0.09–0.99; P  = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis. Conclusions Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.</description><subject>Adjuvant chemotherapy</subject><subject>Adult</subject><subject>Aged</subject><subject>Angiogenesis</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - blood</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer metastasis</subject><subject>Cancer patients</subject><subject>Cancer research</subject><subject>Care and treatment</subject><subject>Cell-Derived Microparticles - genetics</subject><subject>Cell-Derived Microparticles - pathology</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>Clinical Trial</subject><subject>Development and progression</subject><subject>Disease-Free Survival</subject><subject>Endothelium</subject><subject>Endothelium - pathology</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Humans</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Microparticles</subject><subject>Middle Aged</subject><subject>Neoadjuvant Therapy</subject><subject>Oncology</subject><subject>Patient outcomes</subject><subject>Prognosis</subject><subject>Survival</subject><subject>Treatment Outcome</subject><subject>Vascular endothelial growth factor</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1ktFqFDEUhgdR7Fp9AG8kIIg3U5OZyWTiXVlaFQre6HU4m5zspmQmY5IBdx_DJzbLVm1FCSEk-f6fc5K_ql4yesEoFe8So7yTNWWi7nre14dH1Ypx0daiYeJxtaKsF3U_0P6sepbSLaVUCiqfVmeNbDs6DM2q-rF2US8espu2JI3gfZ3cAQ3ByYS8Q-_Ak9HpGGaI2WmPiUAic0TjdA4xkWCJ9m5yuoBhyTqMSMBmjETvcDx6RJj3xIZINhEhZaJh0hjfE5gIfp99iFCM9mULfp9cel49seATvrhbz6uv11df1h_rm88fPq0vb2rN2z7XvGkoBzTCck1ba7oeB-xKUy0aKwBQakkHawe56ShIZmTXiIFDv2HcWDTtefX25DvH8G3BlNXokkbvYcKwJMXkIHvWtEIW9PVf6G1YYqn3SMlGCt5y_ofagkflJhtyBH00VZel5G5gZRbq4h9UGQbLO4cJrSvnDwRv7gl2CD7vUvBLdmFKD0F2AstvpRTRqjm6EeJeMaqOgVGnwKgSGHUMjDoUzau7zpbNiOa34ldCCtCcgFSupi3Ge63_1_Un8yvNog</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>García Garre, Elisa</creator><creator>Luengo Gil, Ginés</creator><creator>Montoro García, Silvia</creator><creator>Gonzalez Billalabeitia, Enrique</creator><creator>Zafra Poves, Marta</creator><creator>García Martinez, Elena</creator><creator>Roldán Schilling, Vanessa</creator><creator>Navarro Manzano, Esther</creator><creator>Ivars Rubio, Alejandra</creator><creator>Lip, Gregory Y. 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H.</au><au>Ayala de la Peña, Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>169</volume><issue>1</issue><spage>83</spage><epage>92</epage><pages>83-92</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><abstract>Purpose Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer. Methods We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1–0.5 μm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA. Results Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy ( P  = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response ( P  = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04–0.87; P  = 0.02) and progression free survival (HR 0.30; 95% CI 0.09–0.99; P  = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis. Conclusions Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>29340882</pmid><doi>10.1007/s10549-017-4656-z</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-6311-920X</orcidid></addata></record>
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subjects Adjuvant chemotherapy
Adult
Aged
Angiogenesis
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer metastasis
Cancer patients
Cancer research
Care and treatment
Cell-Derived Microparticles - genetics
Cell-Derived Microparticles - pathology
Chemotherapy
Clinical outcomes
Clinical Trial
Development and progression
Disease-Free Survival
Endothelium
Endothelium - pathology
Enzyme-linked immunosorbent assay
Female
Humans
Medical prognosis
Medicine
Medicine & Public Health
Metastases
Metastasis
Microparticles
Middle Aged
Neoadjuvant Therapy
Oncology
Patient outcomes
Prognosis
Survival
Treatment Outcome
Vascular endothelial growth factor
title Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis
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