Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis
High mammographic density (HMD) not only confers a significantly increased risk of breast cancer (BC) but also is associated with BCs of more advanced stages. However, it is unclear whether BC progression and metastasis are stimulated by HMD. We investigated whether patient-derived HMD breast tissue...
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| Veröffentlicht in: | Breast cancer research : BCR 2016-10, Vol.18 (1), p.106-106, Article 106 |
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| container_title | Breast cancer research : BCR |
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| creator | Huo, Cecilia W Waltham, Mark Khoo, Christine Fox, Stephen B Hill, Prue Chen, Shou Chew, Grace L Price, John T Nguyen, Chau H Williams, Elizabeth D Henderson, Michael Thompson, Erik W Britt, Kara L |
| description | High mammographic density (HMD) not only confers a significantly increased risk of breast cancer (BC) but also is associated with BCs of more advanced stages. However, it is unclear whether BC progression and metastasis are stimulated by HMD. We investigated whether patient-derived HMD breast tissue could stimulate the progression of MCF10DCIS.com cells compared with patient-matched low mammographic density (LMD) tissue.
Sterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.
HMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.
Our study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions. |
| doi_str_mv | 10.1186/s13058-016-0767-4 |
| format | Article |
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Sterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.
HMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.
Our study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions.</description><identifier>ISSN: 1465-542X</identifier><identifier>ISSN: 1465-5411</identifier><identifier>EISSN: 1465-542X</identifier><identifier>DOI: 10.1186/s13058-016-0767-4</identifier><identifier>PMID: 27776557</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Animals ; Biomarkers, Tumor ; Breast cancer ; Breast Density ; Breast Neoplasms - diagnostic imaging ; Breast Neoplasms - pathology ; Breast Neoplasms - surgery ; Care and treatment ; Cell Line, Tumor ; Complications and side effects ; Diagnosis ; Disease Models, Animal ; Disease Progression ; Female ; Gene mutations ; Health aspects ; Heterografts ; Humans ; Luciferase ; Mammography ; Mammography - methods ; Metastasis ; Mice ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prophylactic Mastectomy ; Risk Factors</subject><ispartof>Breast cancer research : BCR, 2016-10, Vol.18 (1), p.106-106, Article 106</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-9b1320081e65c014a0ec4f359278b875226e2eef8600c56aff6e33cc87617a163</citedby><cites>FETCH-LOGICAL-c494t-9b1320081e65c014a0ec4f359278b875226e2eef8600c56aff6e33cc87617a163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078949/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078949/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27776557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huo, Cecilia W</creatorcontrib><creatorcontrib>Waltham, Mark</creatorcontrib><creatorcontrib>Khoo, Christine</creatorcontrib><creatorcontrib>Fox, Stephen B</creatorcontrib><creatorcontrib>Hill, Prue</creatorcontrib><creatorcontrib>Chen, Shou</creatorcontrib><creatorcontrib>Chew, Grace L</creatorcontrib><creatorcontrib>Price, John T</creatorcontrib><creatorcontrib>Nguyen, Chau H</creatorcontrib><creatorcontrib>Williams, Elizabeth D</creatorcontrib><creatorcontrib>Henderson, Michael</creatorcontrib><creatorcontrib>Thompson, Erik W</creatorcontrib><creatorcontrib>Britt, Kara L</creatorcontrib><title>Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis</title><title>Breast cancer research : BCR</title><addtitle>Breast Cancer Res</addtitle><description>High mammographic density (HMD) not only confers a significantly increased risk of breast cancer (BC) but also is associated with BCs of more advanced stages. However, it is unclear whether BC progression and metastasis are stimulated by HMD. We investigated whether patient-derived HMD breast tissue could stimulate the progression of MCF10DCIS.com cells compared with patient-matched low mammographic density (LMD) tissue.
Sterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.
HMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.
Our study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions.</description><subject>Adult</subject><subject>Animals</subject><subject>Biomarkers, Tumor</subject><subject>Breast cancer</subject><subject>Breast Density</subject><subject>Breast Neoplasms - diagnostic imaging</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - surgery</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Complications and side effects</subject><subject>Diagnosis</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene mutations</subject><subject>Health aspects</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Luciferase</subject><subject>Mammography</subject><subject>Mammography - methods</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Prophylactic Mastectomy</subject><subject>Risk Factors</subject><issn>1465-542X</issn><issn>1465-5411</issn><issn>1465-542X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptkl9rFDEUxQdRbK1-AF8k4IsvsyaTv_MilK2thRYfVPAtZLN3dlNmkjV3ZqHf3ky31lYkDwkn5_zCDaeq3jK6YMyoj8g4laamTNVUK12LZ9UxE0rWUjQ_nz86H1WvEG8oZdpI87I6arTWSkp9XOVrNwxpk91uG7zr-1uyhohAttPgIlllcDiSMSBOQHAMw9S7EZBcL88ZPVteflv4NJBdLgRADCmSMZEQ9w7DHkgPs4TExTUZYCyoouPr6kXneoQ39_tJ9eP88_fll_rq68Xl8vSq9qIVY92uGG8oNQyU9JQJR8GLjsu20WZltGwaBQ1AZxSlXirXdQo4995oxbRjip9Unw7c3bQaYO0hjtn1dpfD4PKtTS7YpzcxbO0m7a2k2rSiLYAP94Ccfk2Aox0Ceuh7FyFNaJnhUnKuVVOs7_-x3qQpxzLenctIKTT769q4HmyIXSrv-hlqT4WmsqWsnVmL_7jKWsMQfIrQhaI_CbBDwOeEmKF7mJFROxfFHopiS1HsXBQrSubd4895SPxpBv8NZmm5Ng</recordid><startdate>20161025</startdate><enddate>20161025</enddate><creator>Huo, Cecilia W</creator><creator>Waltham, Mark</creator><creator>Khoo, Christine</creator><creator>Fox, Stephen B</creator><creator>Hill, Prue</creator><creator>Chen, Shou</creator><creator>Chew, Grace L</creator><creator>Price, John T</creator><creator>Nguyen, Chau H</creator><creator>Williams, Elizabeth D</creator><creator>Henderson, Michael</creator><creator>Thompson, Erik W</creator><creator>Britt, Kara L</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161025</creationdate><title>Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis</title><author>Huo, Cecilia W ; Waltham, Mark ; Khoo, Christine ; Fox, Stephen B ; Hill, Prue ; Chen, Shou ; Chew, Grace L ; Price, John T ; Nguyen, Chau H ; Williams, Elizabeth D ; Henderson, Michael ; Thompson, Erik W ; Britt, Kara L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-9b1320081e65c014a0ec4f359278b875226e2eef8600c56aff6e33cc87617a163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Biomarkers, Tumor</topic><topic>Breast cancer</topic><topic>Breast Density</topic><topic>Breast Neoplasms - diagnostic imaging</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - surgery</topic><topic>Care and treatment</topic><topic>Cell Line, Tumor</topic><topic>Complications and side effects</topic><topic>Diagnosis</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gene mutations</topic><topic>Health aspects</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Luciferase</topic><topic>Mammography</topic><topic>Mammography - methods</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Prophylactic Mastectomy</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huo, Cecilia W</creatorcontrib><creatorcontrib>Waltham, Mark</creatorcontrib><creatorcontrib>Khoo, Christine</creatorcontrib><creatorcontrib>Fox, Stephen B</creatorcontrib><creatorcontrib>Hill, Prue</creatorcontrib><creatorcontrib>Chen, Shou</creatorcontrib><creatorcontrib>Chew, Grace L</creatorcontrib><creatorcontrib>Price, John T</creatorcontrib><creatorcontrib>Nguyen, Chau H</creatorcontrib><creatorcontrib>Williams, Elizabeth D</creatorcontrib><creatorcontrib>Henderson, Michael</creatorcontrib><creatorcontrib>Thompson, Erik W</creatorcontrib><creatorcontrib>Britt, Kara L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Breast cancer research : BCR</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huo, Cecilia W</au><au>Waltham, Mark</au><au>Khoo, Christine</au><au>Fox, Stephen B</au><au>Hill, Prue</au><au>Chen, Shou</au><au>Chew, Grace L</au><au>Price, John T</au><au>Nguyen, Chau H</au><au>Williams, Elizabeth D</au><au>Henderson, Michael</au><au>Thompson, Erik W</au><au>Britt, Kara L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis</atitle><jtitle>Breast cancer research : BCR</jtitle><addtitle>Breast Cancer Res</addtitle><date>2016-10-25</date><risdate>2016</risdate><volume>18</volume><issue>1</issue><spage>106</spage><epage>106</epage><pages>106-106</pages><artnum>106</artnum><issn>1465-542X</issn><issn>1465-5411</issn><eissn>1465-542X</eissn><abstract>High mammographic density (HMD) not only confers a significantly increased risk of breast cancer (BC) but also is associated with BCs of more advanced stages. However, it is unclear whether BC progression and metastasis are stimulated by HMD. We investigated whether patient-derived HMD breast tissue could stimulate the progression of MCF10DCIS.com cells compared with patient-matched low mammographic density (LMD) tissue.
Sterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.
HMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.
Our study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27776557</pmid><doi>10.1186/s13058-016-0767-4</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Animals Biomarkers, Tumor Breast cancer Breast Density Breast Neoplasms - diagnostic imaging Breast Neoplasms - pathology Breast Neoplasms - surgery Care and treatment Cell Line, Tumor Complications and side effects Diagnosis Disease Models, Animal Disease Progression Female Gene mutations Health aspects Heterografts Humans Luciferase Mammography Mammography - methods Metastasis Mice Middle Aged Mutation Neoplasm Invasiveness Neoplasm Metastasis Prophylactic Mastectomy Risk Factors |
| title | Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis |
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