Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis

Cecilia W. Huo, Mark Waltham, Christine Khoo, Stephen B. Fox, Prue Hill, Shou Chen, Grace L. Chew, John T. Price, Chau H. Nguyen, Elizabeth D. Williams, Michael Henderson, Erik W. Thompson, Kara L. Britt

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Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number106
JournalBreast Cancer Research
Volume18
Issue number1
DOIs
Publication statusPublished - 25 Oct 2016

Keywords

  • Breast cancer
  • Mammographic density
  • MCF10DCIS.com
  • Murine biochamber

Cite this

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. / Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis. In: Breast Cancer Research. 2016 ; Vol. 18, No. 1.
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title = "Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis",
abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
keywords = "Breast cancer, Mammographic density, MCF10DCIS.com, Murine biochamber",
author = "Huo, {Cecilia W.} and Mark Waltham and Christine Khoo and Fox, {Stephen B.} and Prue Hill and Shou Chen and Chew, {Grace L.} and Price, {John T.} and Nguyen, {Chau H.} and Williams, {Elizabeth D.} and Michael Henderson and Thompson, {Erik W.} and Britt, {Kara L.}",
year = "2016",
month = "10",
day = "25",
doi = "10.1186/s13058-016-0767-4",
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Huo, CW, Waltham, M, Khoo, C, Fox, SB, Hill, P, Chen, S, Chew, GL, Price, JT, Nguyen, CH, Williams, ED, Henderson, M, Thompson, EW & Britt, KL 2016, 'Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis', Breast Cancer Research, vol. 18, no. 1, 106. https://doi.org/10.1186/s13058-016-0767-4

Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis. / 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.

In: Breast Cancer Research, Vol. 18, No. 1, 106, 25.10.2016.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis

AU - Huo, Cecilia W.

AU - Waltham, Mark

AU - Khoo, Christine

AU - Fox, Stephen B.

AU - Hill, Prue

AU - Chen, Shou

AU - Chew, Grace L.

AU - Price, John T.

AU - Nguyen, Chau H.

AU - Williams, Elizabeth D.

AU - Henderson, Michael

AU - Thompson, Erik W.

AU - Britt, Kara L.

PY - 2016/10/25

Y1 - 2016/10/25

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - Breast cancer

KW - Mammographic density

KW - MCF10DCIS.com

KW - Murine biochamber

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U2 - 10.1186/s13058-016-0767-4

DO - 10.1186/s13058-016-0767-4

M3 - Article

VL - 18

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

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