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Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis

BACKGROUND: Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm(2), TDLU span (µm), and number of acini/TDLU, and that these metric...

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Autores principales: Davis Lynn, Brittny C., Lord, Brittany D., Cora, Renata, Pfeiffer, Ruth M., Lawrence, Scott, Zirpoli, Gary, Bethea, Traci N., Palmer, Julie R., Gierach, Gretchen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9720909/
https://www.ncbi.nlm.nih.gov/pubmed/36471360
http://dx.doi.org/10.1186/s13058-022-01577-1
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author Davis Lynn, Brittny C.
Lord, Brittany D.
Cora, Renata
Pfeiffer, Ruth M.
Lawrence, Scott
Zirpoli, Gary
Bethea, Traci N.
Palmer, Julie R.
Gierach, Gretchen L.
author_facet Davis Lynn, Brittny C.
Lord, Brittany D.
Cora, Renata
Pfeiffer, Ruth M.
Lawrence, Scott
Zirpoli, Gary
Bethea, Traci N.
Palmer, Julie R.
Gierach, Gretchen L.
author_sort Davis Lynn, Brittny C.
collection PubMed
description BACKGROUND: Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm(2), TDLU span (µm), and number of acini/TDLU, and that these metrics may be elevated in the normal breast tissue of women diagnosed with triple-negative (TN) compared with luminal A breast tumors. It is unknown whether this relationship exists in Black women, who have the highest incidence of TN breast cancer and the highest overall breast cancer mortality rate. We examined relationships between TDLU metrics and breast cancer molecular subtype among breast cancer cases in the Black Women’s Health Study (BWHS). METHODS: We assessed quantitative TDLU metrics (TDLU count/100mm(2), TDLU span (µm), and number of acini/TDLU) in digitized 247 hematoxylin and eosin-stained adjacent normal tissue sections from 223 BWHS breast cancer cases, including 65 triple negative (TN) cancers (estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor-2 (HER2) negative) and 158 luminal A cancers (ER positive, HER2 negative). We evaluated associations of least square mean TDLU metrics adjusted for age and body mass index (BMI) with patient and clinical characteristics. In logistic regression models, we evaluated associations between TDLU metrics and breast cancer subtype, adjusting for age, BMI, and tumor size. RESULTS: Older age and higher BMI were associated with lower TDLU metrics and larger tumor size and lymph node invasion with higher TDLU metrics. The odds of TN compared with luminal A breast cancer increased with increasing tertiles of TDLU metrics, with odds ratios (95% confidence intervals) for tertile 3 versus tertile 1 of 2.18 (0.99, 4.79), 2.77 (1.07, 7.16), and 1.77 (0.79, 3.98) for TDLU count, TDLU span, and acini count/TDLU, respectively. CONCLUSION: Associations of TDLU metrics with breast cancer subtypes in the BWHS are consistent with previous studies of White and Asian women, demonstrating reduced TDLU involution in TN compared with luminal A breast cancers. Further investigation is needed to understand the factors that influence TDLU involution and the mechanisms that mediate TDLU involution and breast cancer subtype. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01577-1.
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spelling pubmed-97209092022-12-06 Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis Davis Lynn, Brittny C. Lord, Brittany D. Cora, Renata Pfeiffer, Ruth M. Lawrence, Scott Zirpoli, Gary Bethea, Traci N. Palmer, Julie R. Gierach, Gretchen L. Breast Cancer Res Research BACKGROUND: Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm(2), TDLU span (µm), and number of acini/TDLU, and that these metrics may be elevated in the normal breast tissue of women diagnosed with triple-negative (TN) compared with luminal A breast tumors. It is unknown whether this relationship exists in Black women, who have the highest incidence of TN breast cancer and the highest overall breast cancer mortality rate. We examined relationships between TDLU metrics and breast cancer molecular subtype among breast cancer cases in the Black Women’s Health Study (BWHS). METHODS: We assessed quantitative TDLU metrics (TDLU count/100mm(2), TDLU span (µm), and number of acini/TDLU) in digitized 247 hematoxylin and eosin-stained adjacent normal tissue sections from 223 BWHS breast cancer cases, including 65 triple negative (TN) cancers (estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor-2 (HER2) negative) and 158 luminal A cancers (ER positive, HER2 negative). We evaluated associations of least square mean TDLU metrics adjusted for age and body mass index (BMI) with patient and clinical characteristics. In logistic regression models, we evaluated associations between TDLU metrics and breast cancer subtype, adjusting for age, BMI, and tumor size. RESULTS: Older age and higher BMI were associated with lower TDLU metrics and larger tumor size and lymph node invasion with higher TDLU metrics. The odds of TN compared with luminal A breast cancer increased with increasing tertiles of TDLU metrics, with odds ratios (95% confidence intervals) for tertile 3 versus tertile 1 of 2.18 (0.99, 4.79), 2.77 (1.07, 7.16), and 1.77 (0.79, 3.98) for TDLU count, TDLU span, and acini count/TDLU, respectively. CONCLUSION: Associations of TDLU metrics with breast cancer subtypes in the BWHS are consistent with previous studies of White and Asian women, demonstrating reduced TDLU involution in TN compared with luminal A breast cancers. Further investigation is needed to understand the factors that influence TDLU involution and the mechanisms that mediate TDLU involution and breast cancer subtype. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01577-1. BioMed Central 2022-12-05 2022 /pmc/articles/PMC9720909/ /pubmed/36471360 http://dx.doi.org/10.1186/s13058-022-01577-1 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Davis Lynn, Brittny C.
Lord, Brittany D.
Cora, Renata
Pfeiffer, Ruth M.
Lawrence, Scott
Zirpoli, Gary
Bethea, Traci N.
Palmer, Julie R.
Gierach, Gretchen L.
Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis
title Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis
title_full Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis
title_fullStr Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis
title_full_unstemmed Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis
title_short Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis
title_sort associations between quantitative measures of tdlu involution and breast tumor molecular subtypes among breast cancer cases in the black women’s health study: a case–case analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9720909/
https://www.ncbi.nlm.nih.gov/pubmed/36471360
http://dx.doi.org/10.1186/s13058-022-01577-1
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