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. 2014 Dec;23(12):2765-73.
doi: 10.1158/1055-9965.EPI-14-0667.

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

Zeina G Khodr  1 , Mark E Sherman  2 , Ruth M Pfeiffer  1 , Gretchen L Gierach  1 , Louise A Brinton  1 , Roni T Falk  1 , Deesha A Patel  1 , Laura M Linville  3 , Daphne Papathomas  1 , Susan E Clare  4 , Daniel W Visscher  5 , Carolyn Mies  6 , Stephen M Hewitt  7 , Anna Maria V Storniolo  8 , Adrian Rosebrock  9 , Jesus J Caban  10 , Jonine D Figueroa  11
Affiliations

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

Zeina G Khodr et al. Cancer Epidemiol Biomarkers Prev. 2014 Dec.

Abstract

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 Ptrends 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. Cancer Epidemiol Biomarkers Prev; 23(12); 2765-73. ©2014 AACR.

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Figures

Figure 1
Figure 1
(A) A representative H&E image showing a woman with limited TDLU involution, as reflected in the increased number of TDLUs and number of acini within the TDLUs. (B) A representative H&E image showing a woman with marked TDLU involution, as reflected by few TDLUs and limited acini content.
See this image and copyright information in PMC

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