TY - JOUR
T1 - Using digital pathology to understand epithelial characteristics of benign breast disease among women undergoing diagnostic image-guided breast biopsy
AU - Mullooly, Maeve
AU - Puvanesarajah, Samantha
AU - Fan, Shaoqi
AU - Pfeiffer, Ruth M.
AU - Olsson, Linnea T.
AU - Hada, Manila
AU - Kirk, Erin L.
AU - Vacek, Pamela M.
AU - Weaver, Donald L.
AU - Shepherd, John
AU - Mahmoudzadeh, Amir
AU - Wang, Jeff
AU - Malkov, Serghei
AU - Johnson, Jason M.
AU - Hewitt, Stephen M.
AU - Herschorn, Sally D.
AU - Sherman, Mark E.
AU - Troester, Melissa A.
AU - Gierach, Gretchen L.
N1 - Funding Information:
The authors are indebted to all the women who generously participated in the BREAST-Stamp Project. The authors are also indebted to the efforts of the physicians, pathologists, nurses, technologists, and interviewers who contributed to this study. The authors thank past research coordinators at The University of Vermont, Claire Bove, Rachael Chicoine, and Patricia Lutton. The authors are grateful to Janet Lawler-Heaver and Kerry Grace Morrissey from Westat for the study management support and Jane Demuth at Information Management Services for data support and analysis. This study was supported by the Intramural Research Program of the NCI at the NIH. This research was also funded in part by the Health Research Board in Ireland (CPFPR-2013-1). This work was also supported by the Avon Foundation, North Carolina University Cancer Research
Funding Information:
Fund, NCI (R01 CA179715), and National Institutes of Environmental Health Sciences U01 ES019472.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - Delayed terminal duct lobular unit (TDLU) involution is associated with elevated mammographic breast density (MD). Both are independent breast cancer risk factors among women with benign breast disease (BBD). Prior digital analyses of normal breast tissues revealed that epithelial nuclear density (END) and TDLU involution are inversely correlated. Accordingly, we examined associations of END, TDLU involution, and MD in BBD clinical biopsies. This study included digitized images of 262 representative image-guided hematoxylin and eosin-stained biopsies from 224 women diagnosed with BBD, enrolled within the cross-sectional BREAST-Stamp project that were visually assessed for TDLU involution (TDLU count/100 mm2, median TDLU span and median acini count per TDLU). A digital algorithm estimated nuclei count per unit epithelial area, or END. Single X-ray absorptiometry of prebiopsy ipsilateral craniocaudal digital mammograms measured global and localized MD surrounding the biopsy region. Adjusted ordinal logistic regression models assessed relationships between tertiles of TDLU and END measures. Analysis of covariance examined mean differences in MD across END tertiles. TDLU measures were positively associated with increasing END tertiles [TDLU count/100 mm2, ORT3vsT1: 3.42, 95% confidence interval (CI), 1.87-6.28; acini count/TDLUT3vsT1, OR: 2.40, 95% CI, 1.39-4.15]. END was significantly associated with localized, but not, global MD. Relationships were most apparent among patients with nonproliferative BBD. These findings suggest that quantitative END reflects different but complementary information to the histologic information captured by visual TDLU and radiologic MD measures and merits continued evaluation in assessing cellularity of breast parenchyma to understand the etiology of BBD.
AB - Delayed terminal duct lobular unit (TDLU) involution is associated with elevated mammographic breast density (MD). Both are independent breast cancer risk factors among women with benign breast disease (BBD). Prior digital analyses of normal breast tissues revealed that epithelial nuclear density (END) and TDLU involution are inversely correlated. Accordingly, we examined associations of END, TDLU involution, and MD in BBD clinical biopsies. This study included digitized images of 262 representative image-guided hematoxylin and eosin-stained biopsies from 224 women diagnosed with BBD, enrolled within the cross-sectional BREAST-Stamp project that were visually assessed for TDLU involution (TDLU count/100 mm2, median TDLU span and median acini count per TDLU). A digital algorithm estimated nuclei count per unit epithelial area, or END. Single X-ray absorptiometry of prebiopsy ipsilateral craniocaudal digital mammograms measured global and localized MD surrounding the biopsy region. Adjusted ordinal logistic regression models assessed relationships between tertiles of TDLU and END measures. Analysis of covariance examined mean differences in MD across END tertiles. TDLU measures were positively associated with increasing END tertiles [TDLU count/100 mm2, ORT3vsT1: 3.42, 95% confidence interval (CI), 1.87-6.28; acini count/TDLUT3vsT1, OR: 2.40, 95% CI, 1.39-4.15]. END was significantly associated with localized, but not, global MD. Relationships were most apparent among patients with nonproliferative BBD. These findings suggest that quantitative END reflects different but complementary information to the histologic information captured by visual TDLU and radiologic MD measures and merits continued evaluation in assessing cellularity of breast parenchyma to understand the etiology of BBD.
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U2 - 10.1158/1940-6207.CAPR-19-0120
DO - 10.1158/1940-6207.CAPR-19-0120
M3 - Article
C2 - 31645342
AN - SCOPUS:85075957569
SN - 1940-6207
VL - 12
SP - 861
EP - 869
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 12
ER -