Abstract:
:Prevention and early detection of breast cancer are the major prophylactic measures taken to reduce the breast cancer related mortality and morbidity. Clinical management of breast cancer largely relies on the efficacy of the breast-conserving surgeries and the subsequent radiation therapy. A key problem that limits the success of these surgeries is the lack of accurate, real-time knowledge about the positive tumor margins in the surgically excised tumors in the operating room. This leads to tumor recurrence and, hence, the need for repeated surgeries. Current intraoperative techniques such as frozen section pathology or touch imprint cytology severely suffer from poor sampling and non-optimal detection sensitivity. Even though histopathology analysis can provide information on positive tumor margins post-operatively (~2-3 days), this information is of no immediate utility in the operating rooms. In this article, we propose a novel image analysis method for tumor margin assessment based on nuclear morphometry and tissue topology and demonstrate its high sensitivity/specificity in preclinical animal model of breast carcinoma. The method relies on imaging nuclear-specific fluorescence in the excised surgical specimen and on extracting nuclear morphometric parameters (size, number, and area fraction) from the spatial distribution of the observed fluorescence in the tissue. We also report the utility of tissue topology in tumor margin assessment by measuring the fractal dimension in the same set of images. By a systematic analysis of multiple breast tissues specimens, we show here that the proposed method is not only accurate (~97% sensitivity and 96% specificity) in thin sections, but also in three-dimensional (3D) thick tissues that mimic the realistic lumpectomy specimens. Our data clearly precludes the utility of nuclear size as a reliable diagnostic criterion for tumor margin assessment. On the other hand, nuclear area fraction addresses this issue very effectively since it is a combination of both nuclear size and count in any given region of the analyzed image, and thus yields high sensitivity and specificity (~97%) in tumor detection. This is further substantiated by an independent parameter, fractal dimension, based on the tissue topology. Although the basic definition of cancer as an uncontrolled cell growth entails a high nuclear density in tumor regions, a simple but systematic exploration of nuclear distribution in thick tissues by nuclear morphometry and tissue topology as performed in this study has never been carried out, to the best of our knowledge. We discuss the practical aspects of implementing this imaging approach in automated tissue sampling scenario where the accuracy of tumor margin assessment can be significantly increased by scanning the entire surgical specimen rather than sampling only a few sections as in current histopathology analysis.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Nyirenda N,Farkas DL,Ramanujan VKdoi
10.1007/s10549-010-0914-zsubject
Has Abstractpub_date
2011-04-01 00:00:00pages
345-54issue
2eissn
0167-6806issn
1573-7217journal_volume
126pub_type
杂志文章abstract::The epidermal growth factor (EGF) is one of several growth factors involved in normal breast epithelial development and tumor proliferation. EGF and EGF-like peptide TGF alpha bind and activate the same membrane receptor protein. This receptor (EGF-R) has been recently studied in breast tumor biopsies and its detectab...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01834623
更新日期:1992-03-01 00:00:00
abstract::Mammographic density is a strong risk factor for breast cancer; however the mechanism that underlies this association is unclear. We hypothesized that measures of energy balance early in life and in adulthood may be associated with mammographic density. We conducted a cross-sectional analysis of 1,398 women in the Nur...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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journal_title:Breast cancer research and treatment
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doi:10.1007/s10549-007-9589-5
更新日期:2008-03-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 历史文章,杂志文章
doi:10.1007/s10549-007-9753-y
更新日期:2008-09-01 00:00:00
abstract::We showed previously that zerumbone (ZER), a sesquiterpene isolated from subtropical ginger, inhibited in vitro (MCF-7 and MDA-MB-231cells) and in vivo (MDA-MB-231 cells) growth of human breast cancer cells in association with apoptosis induction. Here, we investigated the role of Notch receptors in anticancer effects...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3059-7
更新日期:2014-08-01 00:00:00
abstract::This study describes the inhibitory effect of 5 alpha-dihydrotestosterone (5 alpha-DHT) and its precursors testosterone (T) and androst-4-ene-3,17-dione (delta 4-DIONE) on the growth of the estrogen-sensitive human breast cancer cell line ZR-75-1. In the absence of estrogens, cell proliferation measured after a 12-day...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805942
更新日期:1988-10-01 00:00:00
abstract::Paclitaxel and vinorelbine are among the most active new agents in metastatic breast cancer. Both in vitro and in vivo studies have shown that the combined administration of these two microtubule-targeting agents is feasible and worthwhile. Based on the promising preclinical data, patients with metastatic breast cance...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005848921895
更新日期:1998-01-01 00:00:00
abstract::Review of comparative pathology studies of breast cancer among Japanese women and other ethnic groups reveals consistent differences in tumor morphology and host response. Japanese women show lower rates of breast cancer than Caucasian women, a difference that is accounted for by increased rates of this cancer in post...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF02633531
更新日期:1991-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05474-8
更新日期:2020-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9337-2
更新日期:2007-05-01 00:00:00
abstract::While many reports describe health-related quality of life (QOL) among breast cancer survivors, few compare QOL before and after diagnosis and whether changes in QOL substantially differ from changes experienced by all women during aging. QOL was examined in a cohort of female residents of Beaver Dam, Wisconsin, aged ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9653-1
更新日期:2008-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666043
更新日期:1995-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-016-4028-0
更新日期:2017-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-009-0429-7
更新日期:2009-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9561-4
更新日期:2008-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2113-6
更新日期:2012-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-020-05528-2
更新日期:2020-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-004-4262-8
更新日期:2005-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9224-x
更新日期:2006-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/BF01840837
更新日期:1992-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3104-6
更新日期:2014-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2119-0
更新日期:2012-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9721-6
更新日期:2008-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05253-5
更新日期:2019-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3004-9
更新日期:2014-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2442-0
更新日期:2013-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0328-y
更新日期:2010-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4499-7
更新日期:2018-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-5783-x
更新日期:2005-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9275-z
更新日期:2007-01-01 00:00:00