TY - JOUR
T1 - Terminal duct lobular unit involution of the normal breast
T2 - Implications for breast cancer etiology
AU - Figueroa, Jonine D.
AU - Pfeiffer, Ruth M.
AU - Patel, Deesha A.
AU - Linville, Laura
AU - Brinton, Louise A.
AU - Gierach, Gretchen L.
AU - Yang, Xiaohong R.
AU - Papathomas, Daphne
AU - Visscher, Daniel
AU - Mies, Carolyn
AU - Degnim, Amy C.
AU - Anderson, William F.
AU - Hewitt, Stephen
AU - Khodr, Zeina G.
AU - Clare, Susan E.
AU - Storniolo, Anna Maria
AU - Sherman, Mark E.
N1 - Funding Information:
The KTB is supported by the Susan G. Komen, the Breast Cancer Research Foundation, Oracle Giving, and the Catherine Peachey Fund, Inc. This study was supported through funds from the National Cancer Institute, Intramural Research Program.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Background Greater degrees of terminal duct lobular unit (TDLU) involution have been linked to lower breast cancer risk; however, factors that influence this process are poorly characterized. Methods To study this question, we developed three reproducible measures that are inversely associated with TDLU involution: TDLU counts, median TDLU span, and median acini counts/TDLU. We determined factors associated with TDLU involution using normal breast tissues from 1938 participants (1369 premenopausal and 569 postmenopausal) ages 18 to 75 years in the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Multivariable zero-inflated Poisson models were used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) for factors associated with TDLU counts, and multivariable ordinal logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for factors associated with categories of median TDLU span and acini counts/TDLU. Results All TDLU measures started declining in the third age decade (all measures, two-sided Ptrend . .001); and all metrics were statistically significantly lower among postmenopausal women. Nulliparous women demonstrated lower TDLU counts compared with uniparous women (among premenopausal women, RR = 0.79, 95% CI = 0.73 to 0.85; among postmenopausal, RR = 0.67, 95% CI = 0.56 to 0.79); however, rates of age-related TDLU decline were faster among parous women. Other factors were related to specific measures of TDLU involution. Conclusion Morphometric analysis of TDLU involution warrants further evaluation to understand the pathogenesis of breast cancer and assessing its role as a progression marker for women with benign biopsies or as an intermediate endpoint in prevention studies.
AB - Background Greater degrees of terminal duct lobular unit (TDLU) involution have been linked to lower breast cancer risk; however, factors that influence this process are poorly characterized. Methods To study this question, we developed three reproducible measures that are inversely associated with TDLU involution: TDLU counts, median TDLU span, and median acini counts/TDLU. We determined factors associated with TDLU involution using normal breast tissues from 1938 participants (1369 premenopausal and 569 postmenopausal) ages 18 to 75 years in the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Multivariable zero-inflated Poisson models were used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) for factors associated with TDLU counts, and multivariable ordinal logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for factors associated with categories of median TDLU span and acini counts/TDLU. Results All TDLU measures started declining in the third age decade (all measures, two-sided Ptrend . .001); and all metrics were statistically significantly lower among postmenopausal women. Nulliparous women demonstrated lower TDLU counts compared with uniparous women (among premenopausal women, RR = 0.79, 95% CI = 0.73 to 0.85; among postmenopausal, RR = 0.67, 95% CI = 0.56 to 0.79); however, rates of age-related TDLU decline were faster among parous women. Other factors were related to specific measures of TDLU involution. Conclusion Morphometric analysis of TDLU involution warrants further evaluation to understand the pathogenesis of breast cancer and assessing its role as a progression marker for women with benign biopsies or as an intermediate endpoint in prevention studies.
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U2 - 10.1093/jnci/dju286
DO - 10.1093/jnci/dju286
M3 - Article
C2 - 25274491
AN - SCOPUS:84985021334
VL - 106
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 10
M1 - dju286
ER -