Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ

Abstract Although ductal carcinoma in situ (DCIS) is a non-obligate precursor to ipsilateral invasive breast cancer (iIBC), most DCIS lesions remain indolent. Hence, overdiagnosis and overtreatment of DCIS is a major concern. There is an urgent need for prognostic markers that can distinguish harmle...

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Autores principales:	Mathilde M. M. Almekinders, Michael Schaapveld, Bram Thijssen, Lindy L. Visser, Tycho Bismeijer, Joyce Sanders, Edoardo Isnaldi, Ingrid Hofland, Marjolijn Mertz, Lodewyk F. A. Wessels, Annegien Broeks, Erik Hooijberg, Wilbert Zwart, Esther H. Lips, Grand Challenge PRECISION Consortium, Christine Desmedt, Jelle Wesseling
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0a52b05e321f481ea6b0d325da202d72
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spelling	oai:doaj.org-article:0a52b05e321f481ea6b0d325da202d722021-12-02T17:03:56ZBreast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ10.1038/s41523-021-00232-w2374-4677https://doaj.org/article/0a52b05e321f481ea6b0d325da202d722021-03-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00232-whttps://doaj.org/toc/2374-4677Abstract Although ductal carcinoma in situ (DCIS) is a non-obligate precursor to ipsilateral invasive breast cancer (iIBC), most DCIS lesions remain indolent. Hence, overdiagnosis and overtreatment of DCIS is a major concern. There is an urgent need for prognostic markers that can distinguish harmless from potentially hazardous DCIS. We hypothesised that features of the breast adipose tissue may be associated with risk of subsequent iIBC. We performed a case–control study nested in a population-based DCIS cohort, consisting of 2658 women diagnosed with primary DCIS between 1989 and 2005, uniformly treated with breast conserving surgery (BCS) alone. We assessed breast adipose features with digital pathology (HALO®, Indica Labs) and related these to iIBC risk in 108 women that developed subsequent iIBC (cases) and 168 women who did not (controls) by conditional logistic regression, accounting for clinicopathological and immunohistochemistry variables. Large breast adipocyte size was significantly associated with iIBC risk (odds ratio (OR) 2.75, 95% confidence interval (95% CI) = 1.25–6.05). High cyclooxygenase (COX)-2 protein expression in the DCIS cells was also associated with subsequent iIBC (OR 3.70 (95% CI = 1.59–8.64). DCIS with both high COX-2 expression and large breast adipocytes was associated with a 12-fold higher risk (OR 12.0, 95% CI = 3.10–46.3, P < 0.001) for subsequent iIBC compared with women with smaller adipocyte size and low COX-2 expression. Large breast adipocytes combined with high COX-2 expression in DCIS is associated with a high risk of subsequent iIBC. Besides COX-2, adipocyte size has the potential to improve clinical management in patients diagnosed with primary DCIS.Mathilde M. M. AlmekindersMichael SchaapveldBram ThijssenLindy L. VisserTycho BismeijerJoyce SandersEdoardo IsnaldiIngrid HoflandMarjolijn MertzLodewyk F. A. WesselsAnnegien BroeksErik HooijbergWilbert ZwartEsther H. LipsGrand Challenge PRECISION ConsortiumChristine DesmedtJelle WesselingNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mathilde M. M. Almekinders Michael Schaapveld Bram Thijssen Lindy L. Visser Tycho Bismeijer Joyce Sanders Edoardo Isnaldi Ingrid Hofland Marjolijn Mertz Lodewyk F. A. Wessels Annegien Broeks Erik Hooijberg Wilbert Zwart Esther H. Lips Grand Challenge PRECISION Consortium Christine Desmedt Jelle Wesseling Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ
description	Abstract Although ductal carcinoma in situ (DCIS) is a non-obligate precursor to ipsilateral invasive breast cancer (iIBC), most DCIS lesions remain indolent. Hence, overdiagnosis and overtreatment of DCIS is a major concern. There is an urgent need for prognostic markers that can distinguish harmless from potentially hazardous DCIS. We hypothesised that features of the breast adipose tissue may be associated with risk of subsequent iIBC. We performed a case–control study nested in a population-based DCIS cohort, consisting of 2658 women diagnosed with primary DCIS between 1989 and 2005, uniformly treated with breast conserving surgery (BCS) alone. We assessed breast adipose features with digital pathology (HALO®, Indica Labs) and related these to iIBC risk in 108 women that developed subsequent iIBC (cases) and 168 women who did not (controls) by conditional logistic regression, accounting for clinicopathological and immunohistochemistry variables. Large breast adipocyte size was significantly associated with iIBC risk (odds ratio (OR) 2.75, 95% confidence interval (95% CI) = 1.25–6.05). High cyclooxygenase (COX)-2 protein expression in the DCIS cells was also associated with subsequent iIBC (OR 3.70 (95% CI = 1.59–8.64). DCIS with both high COX-2 expression and large breast adipocytes was associated with a 12-fold higher risk (OR 12.0, 95% CI = 3.10–46.3, P < 0.001) for subsequent iIBC compared with women with smaller adipocyte size and low COX-2 expression. Large breast adipocytes combined with high COX-2 expression in DCIS is associated with a high risk of subsequent iIBC. Besides COX-2, adipocyte size has the potential to improve clinical management in patients diagnosed with primary DCIS.
format	article
author	Mathilde M. M. Almekinders Michael Schaapveld Bram Thijssen Lindy L. Visser Tycho Bismeijer Joyce Sanders Edoardo Isnaldi Ingrid Hofland Marjolijn Mertz Lodewyk F. A. Wessels Annegien Broeks Erik Hooijberg Wilbert Zwart Esther H. Lips Grand Challenge PRECISION Consortium Christine Desmedt Jelle Wesseling
author_facet	Mathilde M. M. Almekinders Michael Schaapveld Bram Thijssen Lindy L. Visser Tycho Bismeijer Joyce Sanders Edoardo Isnaldi Ingrid Hofland Marjolijn Mertz Lodewyk F. A. Wessels Annegien Broeks Erik Hooijberg Wilbert Zwart Esther H. Lips Grand Challenge PRECISION Consortium Christine Desmedt Jelle Wesseling
author_sort	Mathilde M. M. Almekinders
title	Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ
title_short	Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ
title_full	Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ
title_fullStr	Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ
title_full_unstemmed	Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ
title_sort	breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0a52b05e321f481ea6b0d325da202d72
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Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ

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