Circulating sex hormones and terminal duct lobular unit involution of the normal breast

Zeina G. Khodr, Mark E. Sherman, Ruth M. Pfeiffer, Gretchen L. Gierach, Louise A. Brinton, Roni T. Falk, Deesha A. Patel, Laura M. Linville, Daphne Papathomas, Susan E. Clare, Daniel W. Visscher, Carolyn Mies, Stephen M. Hewitt, Anna Maria V. Storniolo, Adrian Rosebrock, Jesus J. Caban, Jonine D. Figueroa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011).

Methods: We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and Prends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders.

Results: Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07-1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95% CI: 0.72-0.89; Ptrend < 0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32-1.97; Ptrend < 0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09-1.59; Ptrend = 0.0043) were associated with higher TDLU counts.

Conclusions: These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution.

Impact: Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis.

Original languageEnglish (US)
Pages (from-to)2765-2773
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Issue number12
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • General Medicine


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